Ovarian Cancer, Solid Tumor, Triple-negative Breast Cancer, Urothelial Carcinoma
Conditions
Brief summary
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).
Interventions
DRUGRucaparib
Rucaparib will be administered per schedule specified in the arm description.
DRUGLucitanib
Lucitanib will be administered per schedule specified in the arm description.
DRUGSacituzumab govitecan
Sacituzumab govitecan will be administered per schedule specified in the arm description.
Sponsors
Gilead Sciences
pharmaand GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Pre-assignment details
The study was planned to be conducted in 2 phases: Phase 1b and Phase 2. Enrollment was terminated before Phase 1b was complete, due to Sponsor's decision to discontinue development of the combination of rucaparib and sacituzumab govitecan. Hence, Phase 2 portion of the study was not conducted.
Participants by arm
| Arm | Count |
|---|---|
| Arm A1: Rucaparib 300 mg BID and Lucitanib 4 mg QD Participants received oral rucaparib 300 mg BID and oral lucitanib 4 mg QD continuously in 28-day cycles. | 6 |
| Arm A2: Rucaparib 400 mg BID and Lucitanib 4 mg QD Participants received oral rucaparib 400 mg BID and oral lucitanib 4 mg QD continuously in 28-day cycles. | 4 |
| Arm A3: Rucaparib 400 mg BID and Lucitanib 6 mg QD Participants received oral rucaparib 400 mg BID and oral lucitanib 6 mg QD continuously in 28-day cycles. | 3 |
| Arm A4: Rucaparib 600 mg BID and Lucitanib 6 mg QD Participants received oral rucaparib 600 mg BID and oral lucitanib 6 mg QD continuously in 28-day cycles. | 6 |
| Arm B1: Rucaparib 300 mg BID and Sacituzumab Govitecan Participants received oral rucaparib 300 mg BID, administered continuously, in combination with IV sacituzumab govitecan 6 mg/kg administration on Day 1 and Day 8 of a 21-day cycle. | 3 |
| Arm B2: Rucaparib 300 mg QD and Sacituzumab Govitecan Participants received oral rucaparib 300 mg QD, administered continuously, in combination with IV sacituzumab govitecan 6 mg/kg administration on Day 1 and Day 8 of a 21-day cycle. | 3 |
| Total | 25 |
Baseline characteristics
| Characteristic | Arm A1: Rucaparib 300 mg BID and Lucitanib 4 mg QD | Arm A2: Rucaparib 400 mg BID and Lucitanib 4 mg QD | Arm A3: Rucaparib 400 mg BID and Lucitanib 6 mg QD | Arm A4: Rucaparib 600 mg BID and Lucitanib 6 mg QD | Arm B1: Rucaparib 300 mg BID and Sacituzumab Govitecan | Arm B2: Rucaparib 300 mg QD and Sacituzumab Govitecan | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 3 Participants | 0 Participants | 6 Participants | 3 Participants | 2 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 2 Participants | 4 Participants | 3 Participants | 3 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 5 Participants | 3 Participants | 2 Participants | 4 Participants | 2 Participants | 3 Participants | 19 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 2 Participants | 5 Participants | 2 Participants | 3 Participants | 19 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 4 | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 6 / 6 | 4 / 4 | 3 / 3 | 6 / 6 | 3 / 3 | 3 / 3 |
| serious Total, serious adverse events | 3 / 6 | 0 / 4 | 0 / 3 | 2 / 6 | 2 / 3 | 1 / 3 |
Outcome results
Primary
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)
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.
Time frame: From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years
Population: Due to Sponsor's decision to discontinue development of the combination of rucaparib and sacituzumab govitecan, the study was terminated before Phase 1b was complete, and Phase 2 portion of the study was not conducted. Hence, the data for this outcome measure could not be collected and analyzed.
Secondary
Duration of Response (DOR) (Phase 2)
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.
Time frame: From the date of first best response to disease progression or death, whichever occurs first, assessed up to 2 years
Population: Due to Sponsor's decision to discontinue development of the combination of rucaparib and sacituzumab govitecan, the study was terminated before Phase 1b was complete, and Phase 2 portion of the study was not conducted. Hence, the data for this outcome measure could not be collected and analyzed.
Secondary
Number of Participants With Objective Response, as Assessed by the Investigator Per RECIST v1.1 (Phase 1b)
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.
Time frame: From the first dose of study drug until the date of documented response to treatment, assessed up to 2 years
Population: Efficacy population included all participants who had received at least 1 dose of rucaparib or the second study drug and who had measurable disease per RECIST v1.1 at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A1: Rucaparib 300 mg BID and Lucitanib 4 mg QD | Number of Participants With Objective Response, as Assessed by the Investigator Per RECIST v1.1 (Phase 1b) | 1 Participants |
| Arm A2: Rucaparib 400 mg BID and Lucitanib 4 mg QD | Number of Participants With Objective Response, as Assessed by the Investigator Per RECIST v1.1 (Phase 1b) | 0 Participants |
| Arm A3: Rucaparib 400 mg BID and Lucitanib 6 mg QD | Number of Participants With Objective Response, as Assessed by the Investigator Per RECIST v1.1 (Phase 1b) | 0 Participants |
| Arm A4: Rucaparib 600 mg BID and Lucitanib 6 mg QD | Number of Participants With Objective Response, as Assessed by the Investigator Per RECIST v1.1 (Phase 1b) | 0 Participants |
| Arm B1: Rucaparib 300 mg BID and Sacituzumab Govitecan | Number of Participants With Objective Response, as Assessed by the Investigator Per RECIST v1.1 (Phase 1b) | 1 Participants |
| Arm B2: Rucaparib 300 mg QD and Sacituzumab Govitecan | Number of Participants With Objective Response, as Assessed by the Investigator Per RECIST v1.1 (Phase 1b) | 2 Participants |
Secondary
Progression-free Survival (PFS) (Phase 2)
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.
Time frame: From the first dose of study drug to documented radiographic progression or death, whichever occurs first, assessed up to 2 years
Population: Due to Sponsor's decision to discontinue development of the combination of rucaparib and sacituzumab govitecan, the study was terminated before Phase 1b was complete, and Phase 2 portion of the study was not conducted. Hence, the data for this outcome measure could not be collected and analyzed.