Current Investigational New Drug Program Trials

		Current Investigational New Drug Program Trials Current = Active, Planned, Closed after July 01, 2002 This information is intended for use by doctors and other health care professionals. If you are a cancer patient, we recommend that you discuss this information with your doctor, who knows you, and who has the facts about your disease. If you are interested in taking part in a clinical trial, your doctor can help explain how this information may apply to you, and if this is the best treatment option in your particular case. Last Updated: May 13, 2025 PHASE STUDIES Lung Cancer - Non-Small Cell - I242 Ovary - I240 PHASE I STUDIES Other malignancy - I226 PHASE I-II STUDIES Breast - I236 Multiple Sites - I214 PHASE II STUDIES Breast - I237 I239 I241 I241A I241B I241C I241D Lung Cancer - Non-Small Cell - I242A Multiple Sites - I206 I238 I243 Non-Hodgkins Lymphoma - I244 I245 Other malignancy - I228 Ovary - I240A I240B I240C Prostate - I223 I232 I234 I234A I234B I234C I234D I234E I234F I234G PHASE I STUDIES Other malignancy I226 A Phase IB Study of Durvalumab (MEDI4736) With or Without Tremelimumab in Patients With Advanced Incurable Solid Malignancies Given with or without Standard Chemotherapy Regimens Eligibility: Objectives: NCT Registration ID (from clinicaltrials.gov): NCT02537418 Participant: Limited to invited cancer centres only. Status: Closed Activation Date: October 01, 2015 , Closing Date: September 06, 2017 Chairs: (Canada) Dr. Rosalyn Anne Juergens, Juravinski Cancer Centre at Hamilton Health Sciences, 1(905) 387-9711 Ext. 64604 (Canada) Dr. Desiree Hao, Tom Baker Cancer Centre, 1(403) 521-3706 PHASE I-II STUDIES Breast I236 A Phase Ib and Open Label Phase II Study of CFI-402257 in Combination with Weekly Paclitaxel in Patients with Advanced/Metastatic HER2-Negative Breast Cancer Eligibility: Histologically and/or cytologically confirmed diagnosis breast cancer that is advanced/metastatic/recurrent or unresectable. Formalin fixed paraffin embedded tissue block available; select number of patients in Phase II must have accessible disease suitable for biopsy. Presence of clinically and/or radiologically documented disease. ECOG 0 or 1. Must have received at least one non-taxane containing chemotherapy regimen for advanced/metastatic disease, unless:relapsed within 6 mos of completion of adjuvant chemo;taxane and/or anthracycline containing adjuvant chemo or;contraindications to chemo other than weekly paclitaxel. Patients may not have had previous TTK/MPS1 inhibitor.Patients with HER2 positive breast cancer not eligible; active or uncontrolled infections, serious illness, significant cardiac or pulmonary disease, history of central nervous system mets or spinal cord compression; concurrent treatment with other investigational drugs; patients treated with full dose warfarin Objectives: Primary: Phase I - To establish the safety and tolerability of CFI-402257 given orally in combination with weekly paclitaxel and to identify the recommended Phase II dose (RP2D) in patients with advanced breast cancer. Phase II: To evaluate the anti-tumour activity of the CFI-402257+Paclitaxel combination when administered at the RP2D by determining Overall Response Rate (ORR). Secondary: To estimate the Clinical Benefit Rate (CBR, defined as CR or PR or stable disease (SD) >16 weeks in duration; to evaluate the safety and tolerability; to explore, if indicated, the PK profile of CFI402257 and paclitaxel. Exploratory: in serial tumour biopsies, explore evidence of pharmacodynamic target effect and estimate CFI402257 levels; evaluate the genomic alterations and other molecular features which may be associated with response and/or clinical benefit NCT Registration ID (from clinicaltrials.gov): NCT03568422 Participant: Limited to invited cancer centres only. Status: Closed Activation Date: October 17, 2018 , Closing Date: April 07, 2022 Chairs: (Canada) Dr. Philippe Bedard, University Health Network, 1(416) 946-4501 Ext. 4534 Multiple Sites I214 A Phase I/II Study of MG1 Maraba/MAGE-A3 (MG1MA3), With and Without Adenovirus Vaccine, With Transgenic MAGE-A3 Insertion (AdMA3) in Patients with Incurable Advanced/Metastatic MAGE-A3-Expressing Solid Tumours Eligibility: Patients with histologically confirmed, unresectable locally advanced/metastatic solid tumour (Phase I - Esophogeal/GEJ/gastric, NSCLC and breast, fallopian tube, bladder, adenocystic, anal, melanoma, periampullary, renal, liver, vulvar and ovarian). Tumour must be MAGE-A3 positive. Patient must have have at least one additional tumour mass amenable to core or excisional biopsy and must consent and be willing to undergo at least 2 core biopsies. Patients must have had a least one prior standard first line therapy for advanced/metastatic disease with adequate wash-out period since last dose. Patients must have measurable disease per RECIST 1.1 and adequate organ function. At least 4 weeks since major surgery or radiation therapy. ECOG 0-1. Age >= 18 years. Objectives: Phase I-To determine the recommended phase II dose/schedule and maximum tolerated dose of MG1MA3 alone, AdMA3 alone and in combination. To determine the safety, tolerability, pharmacokinetics (PK) including viral shedding, viral delivery and replication in the tumour cells and anti-tumour activity. Phase II-To assess the anti-tumour activity as evidenced by response rates and further explore the safety profile, PK, cellular and immune response, changes in tumour biomarkers and evaluate overall survival, time to progression by tumour type. NCT Registration ID (from clinicaltrials.gov): NCT02285816 Participant: Limited to invited cancer centres only. Status: Closed Activation Date: October 31, 2014 , Closing Date: April 11, 2019 Chairs: (Canada) Dr. Derek Jonker, Ottawa Hospital Research Institute, 1(613) 737-7700 Ext. 70168 PHASE II STUDIES Breast I237 A Phase II Study of CFI-400945 in Patients with Advanced/Metastatic Breast Cancer Eligibility: Histologically and/or cytologically confirmed diagnosis breast cancer that is advanced/metastatic/recurrent or unresectable and either ER-, PR- and HER2- (COHORT 1) or ER+/PR+, HER2- and PTEN-null (COHORT 2) or ER+/PR+, HER2- and not PTEN-null (COHORT 3). FFPE tissue block available; select number of patients per cohort must have accessible disease suitable for biopsy. Presence of clinically/radiologically documented disease. ECOG 0 or 1. At least 1 prior line of cytotoxic chemotherapy for breast cancer, in any setting, must have included anthracycline and taxane (unless contraindicated). No limit to number of prior regimens. May have received other therapies (i.e. endocrine therapy, immunotherapy, targeted therapies). HER2+ breast cancer not eligible; active or uncontrolled infections, serious illness, significant cardiac or pulmonary disease, history of CNS mets or spinal cord compression; concurrent treatment with other investigational drugs; treated with full dose warfarin. Objectives: Primary: To evaluate the objective response rate of CFI-400945 in patients with unresectable locally recurrent or metastatic breast cancer. Secondary: To estimate the Disease Control Rate (DCR, defined as CR or PR or stable disease (SD) >16 weeks in duration; to evaluate the safety and tolerability; to evaluate pharmacodynamics and cellular effects on tumour cells through paired tumour biopsies. Tertiary: To evaluate somatic genomic alterations and other molecular features (gene or protein expression levels) associated with response and/prolonged stable disease; to evaluate the association between PTEN status and response; to explore mechanisms of acquired resistance to CFI-400945 and clonal evolution in response to CFI-400945 treatment using cfDNA. NCT Registration ID (from clinicaltrials.gov): NCT03624543 Participant: Limited to invited cancer centres only. Status: Closed Activation Date: December 21, 2018 , Closing Date: January 17, 2023 Chairs: (Canada) Dr. Rossanna Pezo-Martin, Odette Cancer Centre, 1(416) 480-4757 (Canada) Dr. David Cescon, University Health Network, 1(416) 946-2245 I239 A Phase II Study of CFI-400945 and Durvalumab in Patients with Advanced/Metastatic Triple Negative Breast Cancer (TNBC) Eligibility: Histologically and/or cytologically confirmed diagnosis of breast cancer that is advanced/metastatic or unresectable and negative for ER, PR and HER2. FFPE tissue block available; select number of patients must have accessible disease suitable for biopsy. Presence of clinically/radiologically documented disease. ECOG 0 or 1. At least 1 prior line of cytotoxic chemotherapy for breast cancer, in any setting, must have included anthracycline and taxane. No limit to number of prior regimens. May have received other therapies (i.e. endocrine therapy, targeted therapies). Must not have received prior immunotherapy. Not permitted: Active or uncontrolled infections, active or prior autoimmune or inflammatory disorders, primary immunodeficiency or allogenic organ transplant, serious illness, untreated or uncontrolled cardiovascular conditions, history of CNS mets or spinal cord compression; concurrent treatment with other investigational drugs, treated with full dose warfar in or growth factors. Objectives: Primary Objectives: To evaluate the objective response rate (RECIST 1.1) of CFI-400945 given with durvalumab. Secondary Objectives: To evaluate Disease Control Rate (DCR, defined as CR or PR or stable disease (SD) > 16 weeks in duration) of CFI-400945 given with durvalumab, to evaluate the immune-related response rate (iRECIST) of CFI-400945 given with durvalumab, to establish the safety and tolerability of CFI-400945 given orally in combination with durvalumab in a q4w schedule and to confirm the recommended phase II dose (RP2D) in patients with metastatic triple negative breast cancer (TNBC), and to assess the pharmacodynamic and immune effects of CFI-400945+durvalumab. NCT Registration ID (from clinicaltrials.gov): NCT04176848 Participant: Limited to invited cancer centres only. Status: Closed Activation Date: December 19, 2019 , Closing Date: April 26, 2022 Chairs: (Canada) Dr. Andrew Robinson, Cancer Centre of Southeastern Ontario at Kingston, 1(613) 549-6666 Ext. 8104 (Canada) Dr. David Cescon, University Health Network, 1(416) 946-2245 I241 A Liquid-biopsy Informed Platform Trial to Evaluate Treatment in CDK4/6-inhibitor Resistant ER+/HER2- Metastatic Breast Cancer Eligibility: Patients (>=18yrs old, ECOG PS 0-1), life expectancy >=3 mo., must have advanced/metastatic ER+/HER2- breast cancer as per ASCO/CAP criteria that have objective progression on first line CDK4/6i+ET. One subsequent line of endocrine or target therapy is allowed. Pts may have received adjuvant/neoadjuvant systemic therapies; palliative cytotoxic chemotherapy is not permissible. All reversible prior toxicity related to prior therapies must have recovered to grade =<1 and have adequate washout. Measurable disease per RECIST 1.1. Consent to release of tissue block and biopsies. Women/men of childbearing potential must have agreed to use an effective contraceptive method. No history of other malignancies or uncontrolled /serious illnesses which would not permit the patient to be managed per protocol. Hypersensitivity to any of the study drug components. No CNS metastases. No pts who are unable to swallow oral meds/have impairment of GI function. No history of non-complia nce. Objectives: Primary: Centrally genotype ctDNA from patients with CDK4/6i+ET resistant ER+/HER2- metastatic breast cancer and evaluate whether biomarker selection improves outcomes as assessed by RECIST 1.1 overall response rate (ORR), or for select studies, clinical benefit rate (CBR). Secondary: Evaluate safety and toxicity of each substudy drug and summarize progression free and overall survival. Exploratory: Create and maintain a tissue/data bank for patients undergoing screening for enrollment to a treatment substudy, evaluate changes in liquid biopsy ctDNA and CTCs as surrogates of treatment outcomes, evaluate potential biomarkers of response, resistance and progression through exploratory corelative studies. NCT Registration ID (from clinicaltrials.gov): NCT05601440 Participant: Limited to invited cancer centres only. Status: Open Activation Date: January 27, 2023 Chairs: (Canada) Dr. David Cescon, University Health Network, 1(416) 946-2245 I241A Liquid-Biopsy Monitoring for Patients not yet Eligible for Screening and Enrollment Eligibility: Patients (>=18yrs old), life expectnacy >=3 mo., must have advanced/metastatic ER+/HER2- breast cancer as per ASCO/CAP criteria that are on or about to initiate active treatment with standard first-line therapy with a CDK4/6 inhibitor combined with an aromatase inhibitor.Pts. who have progressed on, or within 12 mo. of completion of adjuvant therapy with an aromatase inhibitor may be treated with fulvestrant instead of an aromatase inhibitor.. Measurable disease per RECIST 1.1. Consent to release of tissue block and biopsies. Not pregnant or breastfeeding. No history of other malignancies or uncontrolled /serious illnesses which would not permit the patient to be managed per protocol. Hypersensitivity to any of the study drug components. No CNS metastases. No pts who are unable to swallow oral meds/have impairment of GI function. No history of non-compliance. Objectives: Primary: To create and maintain a tissue and data bank including tumour and liquid biopsies and clinical data for patients receiving first line endocrine therapy plus CDK4/6i treatment. Exploratory: To evaluate potential biomarkers of response, resistance and progression through exploratorycorrelative studies using ctDNA and CTCs. Participant: Limited to invited cancer centres only. Status: Open Activation Date: January 27, 2023 Chairs: (Canada) Dr. David Cescon, University Health Network, 1(416) 946-2245 I241B A Phase II Study of RP-6306 in Patients with CDK4/6-Inhibitor Treated ER+HER2- Metastatic Breast Cancer Receiving Gemcitabine Eligibility: Patients must meet the following criteria in addition to the eligibility criteria outlined in IND.241. Pts. must have exhausted all standard endocrine therapies including standard fulvestrant. Must not have had prior treatemt with a WEE1 inhibitor, PKMYT1 inhibitor or gemcitabine. Mean resting QTcF =<450 msec/male and =<470 msec/female. Cannot be receiving treatment with medications that prolong the QT interval and/or strong CYP3A inhibitors or inducers within 14 days prior to first dose of study treatment. Objectives: Primary: To centrally genotype ctDNA from patients with CD4/6i-resistant ER+/HER2- metastatic breast cancer (MBC) and evaluate whether biomarker selection improves outcoems as assessed by RECIST 1.1 ORR. Secondary: To evaluate the safety and toxicity profile of RP-6306 with gemcitabine and to summarize progression free and overall survival. Exploratory Objectives: To evlauate changes in liquid bioposy ctDNA and CTCs as surrogates of treatment outcomes and to evaluate potential biomarkers of response, resistance and progression through exploatory correlative studies using ctDNA, CTCs, tissue-based analyses and radiomics. Participant: Limited to invited cancer centres only. Status: Closed Activation Date: January 27, 2023 , Closing Date: September 10, 2024 Chairs: (Canada) Dr. John Hilton, Ottawa Hospital Research Institute, (613) 737-7700 Ext. 75086 I241C A Phase II Study of Niraparib, A PARP Inhibitor, in Patients with CDK4/6-Inhibitor Treated ER+/HER2- Metastatic Breast Cancer Eligibility: Patients must meet the following criteria in addition to the eligibility criteria outlined in IND.241. Patients may have received prior PARPi therapy, but only in the adjuvant setting provided the treatment-free interval is >12 moinths from date of completion of the PARPi. Patients must be eligible for secondline endocrine therapy with fulvestrant as standard of care. Patients must not have had prior history of PRES. Objectives: Primary: To centrally genotype ctDNA from patients with CDK4/6i-resistant ER+/HER2- metastatic breast cancer (MBC) and evaluate whether biomarker selection improves outcomes as assessed by RECIST 1.1 ORR.. To evaluate the safety and toxicity profile of Nirapirab with fulvestrant and to summarize progression free and overall survival. Exploratory: To evaluate changes in liquid biopsy ctDNA and CTCs as surrogates of treatment outcomes and to evaluate potential biomarkers of response, resistance and progression through exploratory correlative studies using ctDNA, CTCs, tissue-based analyses and radiomics. Participant: Limited to invited cancer centres only. Status: Closed Activation Date: January 27, 2023 , Closing Date: January 22, 2025 Chairs: (Canada) Dr. Stephen Chia, BCCA - Vancouver Cancer Centre, 1(604) 877-6000 Ext. 2752 (Canada) Dr. Nathalie Levasseur, BCCA - Vancouver Cancer Centre, (604) 877-6000 I241D A Phase II Study of Lunresertib Plus Camonsertib in Patients With CDK4/6 Inhibitor Treated ER+/HER2- Metastatic Breast Cancer Eligibility: Patients must meet the following criteria in addition to the eligibility criteria outlined in IND.241. Pts must not be deemed candidates for further standard endocrine therapies. Pts may have recevied a 2nd line endocrine therapy in combination with a targeted therapy, with or without a subsequent line of therapy with fulvestrant. Pts. may not have had prior treatment with a WEE inhibitor, DNA-PK, PKMYT1 inhibitor or ATR inhibitor. Pts. who cannot discontinue the use of proton pump inhibitors, strong CYP3A inhibitors or inducers, or strong P-gp or BCRP inhibitors are not eligible. Objectives: Participant: Limited to invited cancer centres only. Status: Open Activation Date: February 06, 2025 Chairs: (Canada) Dr. David Cescon, University Health Network, 1(416) 946-2245 (Canada) Dr. Philippe Bedard, University Health Network, 1(416) 946-4501 Ext. 4534 Lung Cancer - Non-Small Cell I242A A Phase II Pre-operative Trial of JDQ433 in Patients with Surgically Resectable Non-Small Cell Lung Cancer (NSCLC) Eligibility: Objectives: Participant: Limited to invited cancer centres only. Status: Closed Activation Date: May 26, 2023 , Closing Date: May 08, 2024 Chairs: (Canada) Dr. Normand Blais, CHUM-Centre Hospitalier de l'Universite de Montreal, 1(514) 890-8444 (Canada) Dr. Jonathan Spicer, The Research Institute of the McGill University, (514) 934-1934 Ext. 43050 Multiple Sites I238 A Phase II Study of Durvalumab Substudy A: In Patients who Discontinued Prior Checkpoint Therapy Due to Immune Related Toxicity Substudy B: For Continued Treatment (+/-) Tremelimumab) of Patients Previously Enrolled to Completed CCTG Studies Eligibility: Must live in Canada & received durvalumab +/- tremelimumab, with or without chemo/targeted therapy. Patients who received other PD-1/PD-L1 agents +/- anti-CTLA agents may be eligible, contact CCTG. Had a G3 irAEs that required study drug discontinuation per protocol, selected G4 irAEs, & prolonged G1-2 irAEs where physician/patient wanted to discontinue therapy due to poor tolerability. irAE must have resolved to <= grade 1 or baseline. Completed steroid therapy & have documented CR, PR, or prolonged SD to initial IO therapy. Prior adjuvant/neoadjuvant/consolidation IO is eligible provided a >= 6 mo. treatment free interval prior to enrollment and >= 1 standard of care chemo in the palliative setting (discuss with CCTG if chemo is not SOC or indicated or patient refusal/not eligible). Ineligible if prior G4 non-hematological, non-endocrine irAE, or if required biologic agents to manage irAE, had PD as best response to initial IO, or symptomatic or uncontrolled bra in mets. Objectives: Primary: To determine the safety and toxicity profile of rechallenging with durvalumab in patients who previously discontinued immunotherapy due to irAE. Secondary: To determine the objective response rate (RECIST 1.1 and iRECIST); To evaluate the efficacy of corticosteroids in preventing recurrent or new grade 2 or higher irAEs. Tertiary: To explore PFS and iPFS on rechallenge with durvalumab after progression on initial immunotherapy; To explore blood-based and stool-based biomarkers for irAEs; PD-L1 expression. NCT Registration ID (from clinicaltrials.gov): NCT03847649 Participant: Limited to invited cancer centres only. Status: Open Activation Date: June 07, 2019 Chairs: (Canada) Dr. Peter Ellis, Juravinski Cancer Centre at Hamilton Health Sciences, 1(905) 387-9495 (Canada) Dr. Sara Kristina Taylor, BCCA - Cancer Centre for the Southern Interior, 1(250) 712-3996 I243 A Phase II Study of RP-6306 in Patients with Advanced Cancer Eligibility: Patients (>=18yrs old, ECOG PS0-1), life expectancy >=3 mo., must have advanced/metastatic/recurrent or unresectable cancer, with no curable therapy. All reversible prior toxicity related to prior therapies must have recovered to grade =<1 and have adequate washout. Measurable disease per RECIST 1.1. Consent to release of tissue block and biopsies. Women/men of childbearing potential must have agreed to use an effective contraceptive method. No history of other malignancies or uncontrolled /serious illnesses which would not permit the patient to be managed per protocol. Hypersensitivity to any of the study drug components. No CNS metastases. No pts who are unable to swallow oral meds/have impairment of GI function. No history of non-compliance. Met additional cohort specific eligibility criteria. Objectives: Primary: To determine the response rate of RP-6306 in patients with selected cancers receiving standard agents. Secondary: To determine the safety and tolerability of RP-6306 in patients with selected cancers receiving standard agents; To explore the recommended dose of RP-6306, if indicated. Tertiary: To assess potential biomarkers of response, including but not limited to such as PP2R1A, FBXW7 mutations or CCNE1 amplification / overexpression; To assess efficacy of RP-6306 + FOLFIRI in patients harboring KRAS/TP53/FBXW7 triple mutation; To correlate changes in ctDNA with response.clinical outcomes; To summarize progression-free survival. NCT Registration ID (from clinicaltrials.gov): NCT05605509 Participant: Limited to invited cancer centres only. Status: Open Activation Date: April 17, 2023 Chairs: (Canada) Dr. Eric (Xueyu) Chen, University Health Network, 1(416) 946-2263 (Canada) Dr. Stephanie Lheureux, University Health Network, 1(416) 946-4501 Ext. 2415 (Canada) Dr. Yvette Drew, BCCA - Vancouver Cancer Centre, (604) 877-6000 Ext. 4831 Non-Hodgkins Lymphoma I244 A Phase 2 Study of Ibrutinib Combination Therapy in Transplant Ineligible Individuals with Newly Diagnosed Primary Central Nervous System Lymphoma Eligibility: Patients (?18 y/o, ECOG PS 0-2, 3 if due to PCNSL & expected to reverse with treatment) must have histological/cytological evidence of PCNSL; vitreo-retinal/CSF disease eligible with CNS involvement on MRI. No 2? CNS non Hodgkin lymphoma or significant 3rd space fluid which can?t be drained. Must be ineligible for high-dose chemo & ASCT, fit to receive protocol Tx. Consent to release tumour block. No prior radiation/systemic Tx except corticosteroids for PCNSL. ? 8mg/day of dexamethasone (or equivalent) at enrolment & wean within 7 days of starting Tx. Major surgery ?28 days before enrolment (unless for PCNSL) & wounds healed. Able to swallow oral meds, no known GI impairment. No active Tx for other advanced/metastatic malignancy. No serious illnesses/medical conditions precluding management per protocol, no clinically significant cardiac disease (pts with history of cardiac disease: LVEF ?50%). No anticoagulation with warfarin/equivalent or strong CYP3A inhibitor/ inducer. Objectives: Primary: One year progression-free survival (PFS). Secondary: Overall Response Rate (ORR = CR+CRu+PR) and complete response (CR) rate; 1-year event-free survival (EFS); 2-year PFS; Overall survival (OS); To determine the safety and tolerability of ibrutinib, methotrexate, and rituximab treatment in patients with primary central nervous system lymphoma (PCNSL); To determine the impact on patient related outcomes of ibrutinib, methotrexate, and rituximab treatment in patients with PCNSL - Cognitive functioning, Health-related quality of life (FACT-BR) and cognitive symptoms (FACT-Cog). Tertiary: Baseline and serial plasma and cerebrospinal fluid circulating tumour DNA, correlated with outcomes; Radiomic evaluation of predictors of disease response and relapse NCT Registration ID (from clinicaltrials.gov): NCT05998642 Participant: Limited to invited cancer centres only. Status: Open Activation Date: October 24, 2023 Chairs: (Canada) Dr. Jean-Francois Larouche, CHU de Quebec-Hopital l'Enfant-Jesus (HEJ), 1 (Canada) Dr. Anca Prica, University Health Network, 1(416) 946-4501 Ext. 2249 I245 A PHASE II STUDY OF SONROTOCLAX AND ZANUBRUTINIB IN PATIENTS WITH RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA RECEIVING STANDARD OF CARE CAR-T CELL THERAPY Eligibility: Patients (?18 y/o, ECOG PS 0-2, must have histologically confirmed relapsed or refractory mantle cell lymphoma; eligible for and planning to receive Health Canada approved standard of care CAR-T cell therapy, life expectancy of ?6 months. Must have received at least one line of systemic therapy including a BTKn inhibitor and chemoimmunotherapy. Major surgery ?28 days before enrolment & wounds healed. Able to swallow oral meds, no known GI impairment, no untreated Hep C No active Tx for other advanced/metastatic malignancy. No serious illnesses/medical conditions precluding management per protocol, no clinically significant cardiac disease (pts with history of cardiac disease: LVEF ?50%). No growth factors within 28 days prior to enrollment or strong CYP3A inhibitor/inducer. Objectives: Primary: Determine the complete response rate following receipt of standard of care CAR-T cell therapy, in participants receiving treatment with sonrotoclax and zanubrutinib. Secondary: objective response as assessed by the Lugano Classification [prior to and after standard of care CAR T-cell therapy; To determine duration of CR in participants receiving treatment with sonrotoclax and zanubrutinib, following receipt of standard of care CAR-T cell therapy; To determine progression-free survival and overall survival in participants receiving treatment with sonrotoclax and Zanubrutinib; to determine progression-free survival (PFS) and overall survival (OS) in participants receiving treatment with sonrotoclax and zanubrutinib. Tertiary to determine proportion of participants following treatment with sonrotoclax and zanubrutinib who successfully subsequently receive standard of care. Participant: Limited to invited cancer centres only. Status: Planned Chairs: (Canada) Dr. Diego Villa Restrepo, BCCA - Vancouver Cancer Centre, 1(604) 877-6000 Ext. 2740 (Canada) Dr. Robert Puckrin, Tom Baker Cancer Centre, (403) 944-5222 Ovary I240A A Phase II Study of Durvalumab and BA3011, A CAB-AXL-ADCin Patients with Platinum Resistant High Grade Serous Ovarian Cancer Eligibility: Females of childbearing/reproductive potential must agree to use effective contraception on study and 6 months after last dose of BA3011. AXL-positive tumour in Stage 1. No prior therapy with agents targeting AXL or with a conjugated or unconjugated auristatin derivative / vinca targeting payload. No prior receipt of G-CSF or granulocyte/macrophage colony stimulating factor support 2 week prior to first BA3011 dose. No history of greater than or equal to 3 Grade allergic reactions to monoclonal antibody therapy or known/suspected allergy/ intolerance to any agent given during study. No serious medical conditions i.e; intracerebral arteriovenous malformation, cerebral aneurysm or stroke, history of hepatic encephalopathy; clinically significant ascites, measured by physical examination; active drug or alcohol abuse. Patients must not be using moderate or strong CYP3A inducers or inhibitors, including cannabidiol P-glycoprotein (P-gp) inhibitors or immunosupressants . Objectives: Participant: Limited to invited cancer centres only. Status: Open Activation Date: October 12, 2021 Chairs: (Canada) Dr. Anna Tinker, BCCA - Vancouver Cancer Centre, 1(604) 877-6000 Ext. 2707 I240B A Phase II Study of Durvalumab and BA3021, A CAB-ROR2-ADC in Patients with Platinum Resistant High Grade Serous Ovarian Cancer Eligibility: Females of childbearing/reproductive potential must agree to use effective contraception while on the study and for 6 months after last dose of BA3021. ROR2-postive tumour in Stage 2. No prior therapy with agents targeting ROR2, or with a conjugated or unconjugated auristatin derivative / vinca targeting payload. No prior receipt of G-CSF or granulocyte/macrophage colony stimulating factor support 2 week prior to first BA3021 dose. No history of ? 3 Grade allergic reactions to monoclonal antibody therapy or known/suspected allergy/ intolerance to any agent given during study. No serious medical conditions i.e; intracerebral arteriovenous malformation, cerebral aneurysm or stroke, history of hepatic encephalopathy; clinically significant ascites, as measured by physical examination; active drug or alcohol abuse. No use of moderate or strong CYP3A inducers or inhibitors, including cannabidiol P-glycoprotein (P-gp) inhibitors or immunosupressants. Objectives: See main protocol Participant: Limited to invited cancer centres only. Status: Open Activation Date: October 12, 2021 Chairs: (Canada) Dr. Anna Tinker, BCCA - Vancouver Cancer Centre, 1(604) 877-6000 Ext. 2707 I240C A PHASE II STUDY OF TORIPALIMAB-TPZI (LOQTORZI ?) AND ENB-003, AN ENDOTHELIN B RECEPTOR (ETBR) INHIBITOR IN PATIENTS WITH PLATINUM RESISTANT OR REFRACTORY HIGH GRADE SEROUS OVARIAN CANCER OR CLEAR CELL OVARIAN CARCINOMA Eligibility: Patients must have platinum resistant or platinum refractory high grade serous or clear cell carcinoma of ovarian, fallopian tube or peritoneal origin. Platinum resistant disease defined as progression within 6 months of last platinum containing chemotherapy. Platinum refractory disease defined as progression during the administration of the first or second line of platinum containing chemotherapy. Histological confirmation of the original primary tumour. No limit to the number of prior regimens for platinum sensitive disease. But, patients may not have received more than one cytotoxic chemotherapy regimen for platinum resistant or refractory disease. If applicable, the use effective contraception defined as post-menopausal, surgically sterile (hysterectomy or ovariectomy) or on two forms of birth control while on study and 6 months after last treatment. of ENB-003 and toripalimab. Objectives: For complete list of objectives please refer to the main protocol. For this substudy imRECIST will be explored as a secondary objective. Participant: Limited to invited cancer centres only. Status: Planned Chairs: (USA) Dmitriy Zamarin, Mount Sinai Hospital, (212) 824-7309 Prostate I223 A Phase II Study of Palbociclib, A CDK4/6 Inhibitor, in Patients with Metastatic Castration-Resistant Prostate Cancer Eligibility: Patients (>=18 years old, ECOG PS 0-1) must have histologically confirmed mCRPC with no evidence of small cell/neuroendocrine differentiation. Patients will be pre-screened for CCDN1 amplification and RB1 status. Clinically/radiologically documented disease (measurable or non-measurable). Evidence of biochemical and/or radiological disease progression in the setting of surgical or medical castration. Patients must have received prior hormonal treatment with at least one of abiraterone acetate, enzalutamide, ARN-509 TAK-700 and TOK-001. Prior anti-androgen therapy must have been discontinued >=28 days (>=42 days for bicalutamide) prior to registration. Maximum of one prior regimen of cytotoxic chemotherapy permitted. Prior immunotherapy, vaccines and oncolytic viruses permitted. Prior/concurrent CDK or mTOR inhibitors, strontium-89, systemic corticosteriods equivalent to prednisone >10 mg daily not allowed. Potent/strong CYP3A inhibitors/inducers not allowed. Objectives: PRIMARY - To assess the clinical benefit rate (CBR) of palbociclib in patients with metastatic, castration-resistant prostate cancer (mCRPC). SECONDARY - (1) To determine the effect of palbociclib on PSA decline and time to PSA progression; (2) To determine objective response as determined by RECIST 1.1 criteria; (3) To evaluate the safety and toxicity profile of palbociclib in mCRPC patients. EXPLORATORY - (1) To determine whether CCND1 gain/amplification in plasma cell-free DNA (cfDNA) (+/-RB1 wild type) is predictive of CBR to palbociclib; (2) To evaluate gene copy number variation and mutation profile of cfDNA in patients with mCRPC before and after treatment with palbociclib; (3) To identify potential predictive and prognostic blood-based RNA markers. NCT Registration ID (from clinicaltrials.gov): NCT02905318 Participant: Limited to invited cancer centres only. Status: Closed Activation Date: February 09, 2017 , Closing Date: December 13, 2021 Chairs: (Canada) Dr. Kim Chi, BCCA - Vancouver Cancer Centre, 1(604) 877-6000 Ext. 2746 I234 Prostate Cancer Biomarker Enrichment and Treatment Selection (PC_BETS) Study - Master Screening Protocol Eligibility: Patients (>=18 years old, ECOG PS 0-1) must have histologically confirmed mCRPC with no evidence of small cell/neuroendocrine differentiation. Patients must consent to undergo genomic screening. Clinically/radiologically documented disease (measurable or non-measurable). Evidence of biochemical and/or radiological disease progression in the setting of surgical or medical castration. Patients must have received prior hormonal treatment with at least one of abiraterone acetate, enzalutamide, ARN-509 TAK-700 and TOK-001. Prior anti-androgen therapy must have been discontinued >=28 days (>=42 days for bicalutamide) prior to registration. Maximum of one prior regimen of cytotoxic chemotherapy permitted. Prior immunotherapy, vaccines and oncolytic viruses permitted. Prior/concurrent CDK or mTOR inhibitors, strontium-89, systemic corticosteriods equivalent to prednisone >10 mg daily not allowed. Objectives: Primary Objective - To centrally genotype cfDNA from patients with mCRPC progressing after a "next-generation" AR-pathway inhibitor in order to facilitate accrual to targeted therapy trials and then to assess the clinical benefit rate (CBR), of each Study Drug. Secondary Objectives - To determine the effect of each Study Drug on PSA decline and time to PSA progression. To determine objective response as determined by RECIST 1.1 criteria. To evaluate the safety and toxicity profile of each Study Drug in mCRPC patients. Tertiary Objectives - To obtain cfDNA and non-malignant DNA from peripheral blood clinically annotated with patient disease characteristics and follow-up data to identify potential predictive and prognostic factors and relationship between cfDNA results with clinical presentation. NCT Registration ID (from clinicaltrials.gov): NCT03385655 Participant: Limited to invited cancer centres only. Status: Closed Activation Date: December 12, 2017 , Closing Date: February 27, 2024 Chairs: (Canada) Dr. Kim Chi, BCCA - Vancouver Cancer Centre, 1(604) 877-6000 Ext. 2746 I234A A Phase II Study of AZD1775, A WEE1 Inhibitor, in Patients with Metastatic Castration-Resistant Prostate Cancer - A Sub-Study of IND.234 Eligibility: Patients must meet the following criteria in addition to the eligiblity criteria outlined in IND.234. Patients without history of hypersensitivity to AZD1775 or any of its excipients or who have not received treatment with drugs with a similar mechanism of action. Patients witout any factors that increase the risk of QTc prolongation or risk of arrhythmic events or mean resting corrected QT interval (QTc) <= 470 msec. Patients on drugs with a narrow therapeutic index which are substrates of BRCP, PGP, CYP2C19 or CYP1A2, inhibitors of PGP, and which cannot be discontinued or changed to alternative drugs are not eligible. Objectives: To determine the effect of AZD1775 on PSA decline and time to PSA progression. To determine objective response as determined by RECIST 1.1 criteria. To evaluate the safety and toxicity profile of AZD1775 in mCRPC patients. Tertiary Objectives To obtain cfDNA and non-malignant DNA from peripheral blood clinically annotated with patient disease characteristics and follow-up data to identify potential predictive and prognostic factors and relationship between cfDNA results with clinical presentation. NCT Registration ID (from clinicaltrials.gov): NCT03385655 Participant: Limited to invited cancer centres only. Status: Closed Activation Date: December 12, 2017 , Closing Date: December 08, 2021 Chairs: (Canada) Dr. Michael Kolinsky, Cross Cancer Institute, (780) 432-8762 I234B A Phase II Study of Savolitinib, A CMET Inhibitor, in Patients with Metastatic Castration-Resistant Prostate Cancer - A Sub-Study of IND.234 Eligibility: Patients must meet the following criteria in addition to the eligibility criteria outlined in IND.234.Men of childbearing potential must have agreed to use a highly effective contraceptive method during Study Drug treatment and for 6 months after stopping treatment and should not father a child or donate sperm during this period. Patients with significantly abnormal liver diseases including viral/other hepatitis, current alcohol abuse or cirrhosis are not eligible. Patients in whom strong inducers or inhibitors of CYP3A4 and strong inhibitors of CYP1A2 cannot be discontinued within 2 weeks before the first dose of savolitinib (3 weeks for St John's Wort) are not eligible.. Objectives: To determine the effect of savolitinib on PSA decline and time to PSA progression. To determine objective response as determined by RECIST 1.1 criteria. To evaluate the safety and toxicity profile of savolitinib in mCRPC patients. Tertiary Objectives To obtain cfDNA and non-malignant DNA from peripheral blood clinically annotated with patient disease characteristics and follow-up data to identify potential predictive and prognostic factors and relationship between cfDNA results with clinical presentation. NCT Registration ID (from clinicaltrials.gov): NCT03385655 Participant: Limited to invited cancer centres only. Status: Closed Activation Date: December 12, 2017 , Closing Date: February 27, 2024 Chairs: (Canada) Dr. Som Mukherjee, Juravinski Cancer Centre at Hamilton Health Sciences, 1(905) 387-9495 Ext. 64605 I234C A Phase II Study of Darolutamide (ODM-201) in Patients with Metastatic Castration-Resistant Prostate Cancer Previously Treated with Abiraterone Acetate or Enzalutamide - A Sub-Study of IND.234 Eligibility: Patients must meet the following criteria in addition to the eligiblity criteria outlined in IND.234. Serum potassium within normal limits. Prior abiraterone acetate or enzalutamide but not both. No prior cytotoxic systemic chemotherapy in the CRPC setting. Objectives: To determine the effect of darolutamide on PSA decline and time to PSA progression. To determine objective response as determined by RECIST 1.1 criteria. To evaluate the safety and toxicity profile of darolutamide in mCRPC patients. Tertiary Objectives To obtain cfDNA and non-malignant DNA from peripheral blood clinically annotated with patient disease characteristics and follow-up data to identify potential predictive and prognostic factors and relationship between cfDNA results with clinical presentation. NCT Registration ID (from clinicaltrials.gov): NCT03385655 Participant: Limited to invited cancer centres only. Status: Closed Activation Date: December 12, 2017 , Closing Date: February 27, 2024 Chairs: (Canada) Dr. Michael Ong, Ottawa Hospital Research Institute, 1(613) 737-7700 Ext. 75051 I234E A Phase II Study of Ipatasertib in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Patients with PI3K Pathway Alterations in Circulating Tumour DNA (ctDNA) Eligibility: Patients must meet the following criteria in addition to the eligiblity criteria outlined in IND.234. Patients must have adequate hematologic and organ function (AST <= 1.5 x ULN, fasting glucose <= 8.3 mmol/L, glycated hemoglobin <= 7.5%, serum albumin >= 3.0 g/L). Patients with Type 1 or Type 2 diabetes mellitus requiring insulin at study entry must be on a stable dose of diabetes medication for >=4 weeks. Patients must not have uncontrolled/untreated hypercholesterolemia or hypertriglyceridemia, require chronic therapy or use of food supplements that are strong CYP3A4/5 inducers or inhibitors or sensitive substrates of CYL3A or CYP2D6 with a narrow therapeutic window, or prior treatment with therapeutics with known inhibition of the PI3K pathway (including PI3K inhibitors, AKT inhibitors, and mTOR inhibitors). Objectives: To determine the effect of ipatasertib on PSA decline and time to PSA progression. To determine objective response as determined by RECIST 1.1 criteria. To evaluate the safety and toxicity profile of ipatasertib in mCRPC patients. Participant: Limited to invited cancer centres only. Status: Closed Activation Date: December 27, 2019 , Closing Date: February 27, 2024 Chairs: (Canada) Dr. Kim Chi, BCCA - Vancouver Cancer Centre, 1(604) 877-6000 Ext. 2746 I234F A Phase II Study of Durvalumab and Tremelimumab in Metastatic Castration-Resistant Prostate Cancer Eligibility: Patients must meet the following criteria in addition to the eligiblity criteria outlined in IND.234. Patients must not have received prior immune checkpoint inhibitors (anti-PD-(L)1 and/or anti CTLA-4). Patients may not have active or prior documented autoimmune or inflammatory disorders, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome, rheumatoid arthritis, hypophysitis, uveitis, etc. within the past 3 years except alopecia, Grave's disease vitiligo or psoriasis not requiring systemic treatment within the last 2 years, or hypothyroidism stable on hormone replacement. Patients must not have live attenuated vaccination administered within 30 days prior to enrollment or within 30 days of receiving durvalumab. Objectives: To determine the effect of durvalumab and tremelimumab on PSA decline and time to PSA progression. To determine objective response as determined by iRECIST criteria. To evaluate the safety and toxicity profile of durvalumab and tremelimumab in mCRPC patients. To obtain cfDNA and non-malignant DNA from peripheral blood clinically annotated with patient disease characteristics and follow-up data to identify potential predictive and prognostic factors and relationship between cfDNA results with clinical presentation. Participant: Limited to invited cancer centres only. Status: Closed Activation Date: December 27, 2019 , Closing Date: February 27, 2024 Chairs: (Canada) Dr. Sebastien Hotte, Juravinski Cancer Centre at Hamilton Health Sciences, 1(905) 387-9495 Ext. 64605 PHASE STUDIES Lung Cancer - Non-Small Cell I242 Neoadjuvant Platform Trial in Patients with Surgically Resectable Non-Small Cell Lung Cancer (NSCLC) Eligibility: Histologically confirmed diagnosis of primary NSCLC within 90 days of enrollment to a substudy, according to WHO/ classified as Stage IA2 to IIIA according to the AJCC 8th edition TNM classification with disease that is amenable to anatomical surgical resection. Patients with multistation N2.; must be ? 18 years of age. No prior anticancer therapy for treatment of NSCLC. Patients with a history of NSCLC treated in the curative setting may be eligible but must be discussed with CCTG prior to enrollment, ECOG performance status of 0 or 1; synchronous primary tumours may be eligible if all of the following conditions are met:, surgery must be performed between 2 to 4 weeks following the last dose of neoadjuvant therapy, adequate organ and marrow function. Objectives: To identify promising neoadjuvant treatment regimens for NSCLC for later validation in randomized clinical trials, by evaluating major pathological response rates (MPR). Secondary, to summarize the safety and tolerability of each regimen and to evaluate other indicators of activity such as: Overall response rate (ORR) using RECIST 1.1 (and other criteria such as iRECIST as applicable) for neoadjuvant treatment period; Complete pathological response (cPR) rate; Event-free survival rate at 2 years; and Surgical outcomes, including completeness of surgical resection, extent and access to surgery, extent of perihilar/lobar fibrosis or mediastinal adhesions and tumour downstaging. Exploratory include: To identify potential predictive biomarkers of response and mechanisms of resistance, and explore patient related outcomes (PRO). NCT Registration ID (from clinicaltrials.gov): NCT05714891 Participant: Limited to invited cancer centres only. Status: Closed Activation Date: May 26, 2023 , Closing Date: December 16, 2024 Chairs: (Canada) Dr. Normand Blais, CHUM-Centre Hospitalier de l'Universite de Montreal, 1(514) 890-8444 (Canada) Dr. Jonathan Spicer, The Research Institute of the McGill University, (514) 934-1934 Ext. 43050 Ovary I240 An Immunotherapy Platform Study in Platinum Resistant High Grade Serous Ovarian Cancer (IPROC) Eligibility: Patients (>=18 yrs old, ECOG PS 0-1), life expectancy >= 3 mo., must have platinum resistant high-grade serous carcinoma of ovarian, fallopian tube or peritoneal origin defined as progression within the last 6 mo. of last platinum containing chemo. Histological confirmation of original primary tumour. Measurable disease per RECIST 1.1. No limit on prior regimens for platinum sensitive disease but may not have received more than 1 cytotoxic chemotherapy regimen for platinum-resistant disease. Prior treatment with immune checkpoint inhibitors is allowed provided it was not discontinued due to severe/recurrent severe toxicity. May have received non-cytotoxic therapies excluding the agents targeted by the planned substudy. Consent to pre/on treatment tumour biopsies. No uncontrolled/serious illnesses or medical conditions which would not permit the patient to be managed per protocol. No central nervous system metastases. No prior autoimmune or inflammatory disorders wi thin the past 3 yrs. Objectives: Primary: identify based on objective response rate (ORR) (complete and partial response) using RECIST 1.1, promising immunotherapy combinations for the treatment of high grade serious ovarian cancer for later validation in clinical trials. Secondary: evaluate ORR using iRECIST, determine progression free survival and overall survival of immunotherapy regimens (RECIST 1.1 and iRECIST), examine safety and tolerability of each regimen. Tertiary: explore utility of CA125 as a surrogate of response in patients receiving immunotherapies, identify potential predictive biomarkers/markers of response, generate biomarker and clinical data to identify new immunotherapy strategies/combinations for subsequent evaluation. NCT Registration ID (from clinicaltrials.gov): NCT04918186 Participant: Limited to invited cancer centres only. Status: Open Activation Date: October 12, 2021 Chairs: (Canada) Dr. Helen MacKay, Odette Cancer Centre, 1(416) 480-5145