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

• Rucaparib (Drug), also known as Rubraca, CO-338: Rucaparib will be administered per schedule specified in the arm description.
• Lucitanib (Drug), also known as CO-3810: Lucitanib will be administered per schedule specified in the arm description.
• Sacituzumab govitecan (Drug), also known as IMMU-132: Sacituzumab govitecan will be administered per schedule specified in the arm description.

Primary outcomes

• 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]: Objective response was defined as a documented and confirmed best overall response of complete response (CR) or partial response (PR) as assessed by the investigator. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 millimeters (mm); and normalization of tumor marker level. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Secondary outcomes

• 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]: Duration of response was measured from the date that best response (CR or PR) was first recorded until the first date that disease progression was documented per RECIST v1.1. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm; and normalization of tumor marker level. PR: At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Progressive disease: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression.
• 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]: PFS was measured as the 1+ the number of days from the first dose of study drug to documented radiographic progression, according to RECIST v1.1, as determined by the investigator, or death due to any cause, whichever occurred first. Progressive disease: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression.
• 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]: Objective response was defined as a documented and confirmed best overall response of CR or PR as assessed by the investigator. CR: Disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm; and normalization of tumor marker level. PR: At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

Sex: All, ages: 18 Years to any

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

Participant flow

Outcome results

• 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) (Primary)
• Duration of Response (DOR) (Phase 2) (Secondary)
• Progression-free Survival (PFS) (Phase 2) (Secondary)
• Number of Participants With Objective Response, as Assessed by the Investigator Per RECIST v1.1 (Phase 1b) (Secondary), Count of participants, Participants: Arm A1: Rucaparib 300 mg BID and Lucitanib 4 mg QD 1; Arm A2: Rucaparib 400 mg BID and Lucitanib 4 mg QD 0; Arm A3: Rucaparib 400 mg BID and Lucitanib 6 mg QD 0; Arm A4: Rucaparib 600 mg BID and Lucitanib 6 mg QD 0; Arm B1: Rucaparib 300 mg BID and Sacituzumab Govitecan 1; Arm B2: Rucaparib 300 mg QD and Sacituzumab Govitecan 2

Adverse events

Time frame: From the first dose of study drug up to 2 years

Serious adverse events by term

Other adverse events by term

62 more terms not shown.

Limitations and caveats: The study was terminated due to Sponsor's decision to discontinue development of the combination of rucaparib and sacituzumab govitecan.

• Study Protocol (PDF, 2020-09-01)
• Statistical Analysis Plan (PDF, 2021-09-10)

NIH grants: 2018