A Study to Evaluate Rucaparib in Combination With Other Anticancer Agents in Participants With a Solid Tumor (SEASTAR)

Study Overview
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Brief Summary
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This is an open label, Phase 1b/2 study with multiple treatment arms evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of rucaparib in combination with a second anticancer therapy in participants with an advanced/metastatic solid malignancy (Phase 1b), followed by evaluation of the combination in one or more specific participant populations in an expansion phase (Phase 2 cohorts).

Official Title
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SEASTAR: A Phase 1b/2, Open-label, Parallel Arm Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Oral Rucaparib in Combination With Other Anticancer Agents in Patients With a Solid Tumor

Conditions
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Ovarian Cancer, Triple-negative Breast Cancer, Urothelial Carcinoma, Solid Tumor

Intervention / Treatment
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* Drug: Rucaparib
* Drug: Lucitanib
* Drug: Sacituzumab govitecan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Phase 1b (all arms): Solid tumor, advanced or metastatic, progressed on standard treatment participants in Arm B must have either triple negative breast cancer OR urothelial carcinoma OR ovarian cancer OR have a solid tumor with a deleterious mutation in BRCA1, BRCA2, PALB2, RAD51C or RAD51D Measurable disease per RECIST v1.1 Adequate organ function Eastern Cooperative Oncology Group (ECOG) 0 or 1 Tumor tissue for genomic analysis Exclusion Criteria Phase 1b (all arms): Known history of myelodysplastic syndrome (MDS) Symptomatic and/or untreated central nervous system (CNS) metastases Inclusion Criteria Phase 2 (all arms): Histologically or cytologically confirmed solid tumor, previously treated and measurable per RECIST v1.1, as follows: Arm A: ovarian cancer with gBRCAwt disease, either platinum-sensitive OR platinum-resistant Arm B: Metastatic triple negative breast cancer OR advanced/ metastatic urothelial carcinoma OR relapsed ovarian cancer At least 1 prior line of standard therapy for advanced disease Adequate organ function ECOG 0 or 1 Tumor tissue for genomic analysis Exclusion Criteria Phase 2 (all arms): Prior poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor treatment allowed for participants with ovarian cancer Known history of MDS Symptomatic and/or untreated CNS metastases

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Rucaparib and Lucitanib<br>Participants will receive oral rucaparib twice daily (BID) and oral lucitanib once daily (QD) continuously in 28-day cycles. | Drug: Rucaparib<br>* Rucaparib will be administered per schedule specified in the arm description.<br>* Other names: CO-338;Drug: Lucitanib<br>* Lucitanib will be administered per schedule specified in the arm description.<br>* Other names: CO-3810;|
| Experimental: Arm B: Rucaparib BID and Sacituzumab Govitecan<br>Participants will receive oral rucaparib BID, administered continuously, in combination with intravenous (IV) sacituzumab govitecan administration on Day 1 and Day 8 of a 21-day cycle. | Drug: Rucaparib<br>* Rucaparib will be administered per schedule specified in the arm description.<br>* Other names: CO-338;Drug: Sacituzumab govitecan<br>* Sacituzumab govitecan will be administered per schedule specified in the arm description.<br>* Other names: IMMU-132;|
| Experimental: Arm B: Rucaparib QD and Sacituzumab Govitecan<br>Participants will receive oral rucaparib QD, administered continuously, in combination with IV sacituzumab govitecan administration on Day 1 and Day 8 of a 21-day cycle. | Drug: Rucaparib<br>* Rucaparib will be administered per schedule specified in the arm description.<br>* Other names: CO-338;Drug: Sacituzumab govitecan<br>* Sacituzumab govitecan will be administered per schedule specified in the arm description.<br>* Other names: IMMU-132;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Objective Response, as Assessed by the Investigator Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1 (Phase 2) |  | From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) (Phase 2) |  | From the date of first best response to disease progression or death, whichever occurs first, assessed up to 2 years | 
| Progression-free survival (PFS) (Phase 2) |  | From the first dose of study drug to documented radiographic progression or death, whichever occurs first, assessed up to 2 years | 
| Number of Participants With Objective Response, as Assessed by the Investigator Per RECIST v1.1 (Phase 1b) |  | From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years |