A Study of CPI-0209 in Patients With Advanced Solid Tumors and Lymphomas
- Interventional
- Recruiting
- NCT04104776
Contact Information
A Phase 1/2 Study of CPI-0209 in Patients With Advanced Solid Tumors and Lymphomas
First-in-human, open-label, sequential dose escalation and expansion study of CPI-0209 in patients with advanced solid tumors and lymphomas. CPI-0209 is a small molecule inhibitor of EZH2.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers?
No
Inclusion Criteria:
Phase 2:
- Life expectancy of ≥ 12 weeks
- ECOG 0-1
- Adequate bone marrow function
- Adequate renal function
- Adequate liver function
For Cohort M1, the following criteria should be considered:
- Histologically confirmed locally advanced unresectable or metastatic urothelial carcinoma with predominant urothelial histology
- Histologically confirmed metastatic solid tumor (except ovarian clear cell cancer, endometrial cancer, and pleural or peritoneal mesothelioma)
- Known ARID1A mutation
- Disease progression during or following prior chemotherapy
- Measurable disease per RECIST 1.1
For Cohort M2, the following criteria should be considered:
- Histologically confirmed advanced ovarian clear cell carcinoma
- Known ARID1A mutation
- Received at least 1 line of platinum-based chemotherapy
- Measurable disease per RECIST 1.1
- Patient must have disease progression after previously receiving effective and available standard of care treatment for clear cell ovarian cancer per local clinical practice
For Cohort M3, the following criteria should be considered:
- Histologically or cytologically confirmed recurrent, metastatic, or unresectable endometrial carcinoma
- Known ARID1A mutation
- Received at least 1 line of platinum-based regimen in recurrent/metastatic setting
- Documented microsatellite instability (MSI)-high or deficient mismatch repair (dMMR) tumors should have received, or not be considered eligible for therapy with an anti-PD-1 agent
- Brachytherapy is allowed if completed >12 weeks before the first dose of study drug
- Measurable disease per RECIST 1.1
- Patients must have previously received effective and available standard of care treatment options for endometrial cancer per local clinical practice
For Cohort M4, the following criteria should be considered:
- PTCL or DLBCL with the following criteria:
- PTCL:
- Documented refractory, relapsed, or progressive disease after at least 1 prior line of systemic therapy. Refractory is defined as:
- Failure to achieve CR after first-line therapy
- Failure to reach at least PR after second-line therapy or beyond
- Must have at least 1 prior line of systemic therapy for PTCL.
- Participants must be considered hematopoietic cell transplantation (HCT) ineligible during screening due to disease status (active disease), comorbidities, or other factors; the reason for HCT ineligibility must be clearly documented.
- In the PTCL cohort, participants with anaplastic large cell lymphoma (ALCL) must have prior brentuximab vedotin treatment.
- DLBCL:
- Relapsed or refractory disease following 2 or more prior lines of standard therapy. A minimum of 5 patients with documented GCB-DLBCL with at least 1 EZH2 hotspot mutation will be enrolled.
- Not considered candidates to receive CAR-T or autologous hematopoietic stem cell transplant (ASCT) as assessed by the treating investigator for reasons such as age, underlying comorbidities, or performance status, or due to disease progression after previously received ASCT or CAR-T. The reason for transplant ineligibility must be clearly documented.
- For patients who underwent past ASCT or CAR-T treatment, at least 90 days must have elapsed since the start of the procedure. For all other patients, at least 8 weeks must have elapsed since their most recent systemic anti-DLBCL therapy
For Cohort M5, the following criteria should be considered:
- Pleural or peritoneal relapsed/refractory mesothelioma
- Must have progressed on or after at least 1 prior line of active therapy
- Measurable disease per modified RECIST 1.1
- Known BAP1 loss per immunohistochemistry (IHC) or NGS
For Cohort M6, the following criteria should be considered:
- Have measurable soft-tissue disease
- Documented metastatic disease
- Disease progression while on prior therapies
- Baseline testosterone ≤50 ng/dL (≤2.0 nM) and surgical or ongoing medical castration must be maintained throughout the duration of the study
For Cohort M6, the following criteria should be considered:
- Bone-only disease without nodal disease and no evidence of visceral spread
- Structurally unstable bone lesions concerning for impending fracture
- Prior treatment with:
- First generation AR antagonists within 4 weeks of study treatment
- 5α reductase inhibitors, ketoconazole, estrogens (including DES), or progesterones within 2 weeks of study treatment
- No planned palliative procedures for alleviation of bone pain
Phase 2:
- Life expectancy of ≥ 12 weeks
- ECOG 0-1
- Adequate bone marrow function
- Adequate renal function
- Adequate liver function
For Cohort M1, the following criteria should be considered:
- Histologically confirmed locally advanced unresectable or metastatic urothelial carcinoma with predominant urothelial histology
- Histologically confirmed metastatic solid tumor (except ovarian clear cell cancer, endometrial cancer, and pleural or peritoneal mesothelioma)
- Known ARID1A mutation
- Disease progression during or following prior chemotherapy
- Measurable disease per RECIST 1.1
For Cohort M2, the following criteria should be considered:
- Histologically confirmed advanced ovarian clear cell carcinoma
- Known ARID1A mutation
- Received at least 1 line of platinum-based chemotherapy
- Measurable disease per RECIST 1.1
- Patient must have disease progression after previously receiving effective and available standard of care treatment for clear cell ovarian cancer per local clinical practice
For Cohort M3, the following criteria should be considered:
- Histologically or cytologically confirmed recurrent, metastatic, or unresectable endometrial carcinoma
- Known ARID1A mutation
- Received at least 1 line of platinum-based regimen in recurrent/metastatic setting
- Documented microsatellite instability (MSI)-high or deficient mismatch repair (dMMR) tumors should have received, or not be considered eligible for therapy with an anti-PD-1 agent
- Brachytherapy is allowed if completed >12 weeks before the first dose of study drug
- Measurable disease per RECIST 1.1
- Patients must have previously received effective and available standard of care treatment options for endometrial cancer per local clinical practice
For Cohort M4, the following criteria should be considered:
- PTCL or DLBCL with the following criteria:
- PTCL:
- Documented refractory, relapsed, or progressive disease after at least 1 prior line of systemic therapy. Refractory is defined as:
- Failure to achieve CR after first-line therapy
- Failure to reach at least PR after second-line therapy or beyond
- Must have at least 1 prior line of systemic therapy for PTCL.
- Participants must be considered hematopoietic cell transplantation (HCT) ineligible during screening due to disease status (active disease), comorbidities, or other factors; the reason for HCT ineligibility must be clearly documented.
- In the PTCL cohort, participants with anaplastic large cell lymphoma (ALCL) must have prior brentuximab vedotin treatment.
- DLBCL:
- Relapsed or refractory disease following 2 or more prior lines of standard therapy. A minimum of 5 patients with documented GCB-DLBCL with at least 1 EZH2 hotspot mutation will be enrolled.
- Not considered candidates to receive CAR-T or autologous hematopoietic stem cell transplant (ASCT) as assessed by the treating investigator for reasons such as age, underlying comorbidities, or performance status, or due to disease progression after previously received ASCT or CAR-T. The reason for transplant ineligibility must be clearly documented.
- For patients who underwent past ASCT or CAR-T treatment, at least 90 days must have elapsed since the start of the procedure. For all other patients, at least 8 weeks must have elapsed since their most recent systemic anti-DLBCL therapy
For Cohort M5, the following criteria should be considered:
- Pleural or peritoneal relapsed/refractory mesothelioma
- Must have progressed on or after at least 1 prior line of active therapy
- Measurable disease per modified RECIST 1.1
- Known BAP1 loss per immunohistochemistry (IHC) or NGS
For Cohort M6, the following criteria should be considered:
- Have measurable soft-tissue disease
- Documented metastatic disease
- Disease progression while on prior therapies
- Baseline testosterone ≤50 ng/dL (≤2.0 nM) and surgical or ongoing medical castration must be maintained throughout the duration of the study
For Cohort M6, the following criteria should be considered:
- Bone-only disease without nodal disease and no evidence of visceral spread
- Structurally unstable bone lesions concerning for impending fracture
- Prior treatment with:
- First generation AR antagonists within 4 weeks of study treatment
- 5α reductase inhibitors, ketoconazole, estrogens (including DES), or progesterones within 2 weeks of study treatment
- No planned palliative procedures for alleviation of bone pain
- Lymphoma
- Mesothelioma
- Solid Tumors