A Study of CPI-0209 in Patients With Advanced Tumors

• Status: Recruiting
• Trial end date: 2026-03-01
• Target enrollment: 0
• Participant gender: All

Summary

First-in-human, open-label, sequential dose escalation and expansion study of CPI-0209 in patients with advanced tumors alone and in combination with other therapies. CPI-0209 is a small molecule inhibitor of EZH2.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Constellation Pharmaceuticals
• Treatments: Irinotecan

Criteria

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

• 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:

• Histologically confirmed lymphoma, with relapsed or refractory disease following 2 or more prior lines of standard therapy

• Not considered candidates to receive CAR-T or autologous hematopoietic stem cell transplant (ASCT) as assessed by the treating investigator

• Patients must not have received ASCT or CAR-T treatment for ≥90 days since the start of the procedure OR ≥8 weeks since most recent systemic anti-DLBCL therapy

• At least 1 bi-dimensionally measurable lesion on imaging scan defined as >1.5 cm in its longest dimension

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 C1, the following criteria should be considered:

• Histologically or cytologically confirmed ES-SCLC that relapsed within 6 months after first-line chemotherapy with platinum-etoposide for at least 2 cycles

• Prior immunotherapy is required

• No prior topoisomerase 1 inhibitor

Exclusion Criteria:

• Previous solid organ or allogenic hematopoietic cell transplant

• Known brain metatstases

• Prior EZH2 inhibitor

• Prior systemic anticancer treatment within 4 weeks of study treatment

• Prior radiation therapy within 4 weeks of study treatment

• Prior chemoembolization within 4 weeks of study treatment

• Concomitant medication(s) or food or beverage that are moderate or strong CYP3A inducers or inhibitors within 7 days prior to the first dose of study drug

• Clinically significant cardiovascular disease

• Major surgery within 4 weeks

• GI disorders affecting absorption

• Uncontrolled infection

• Suspected pneumonitis or interstitial lung disease

• Known additional malignancy that is active and/or progressive requiring treatment

• Known HIV or active hepatitis

• Chronic liver disease

• Women of child bearing potential and men with reproductive potential, if they are unwilling to use adequate contraception while on study therapy and for 3 months thereafter

• Patients unwilling or unable to comply with this study protocol

For Cohort C1, the following criteria should be considered:

• Gilbert's disease or known homozygosity for UGT1A1*28 allele

• Prior irinotecan or topotecan therapy

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