A Combination Study of Rucaparib and Atezolizumab in Participants With Advanced Gynecologic Cancers and Triple-Negative Breast Cancer

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• Triple Negative Breast Neoplasms 1,140
• Genital Neoplasms, Female 117

Triple Negative Breast Neoplasms

1,140 studies on the registry are indexed under Triple Negative Breast Neoplasms; 443 are open to participants now.

This study's enrollment of 29 is below the median of 61 across 982 interventional studies indexed under Triple Negative Breast Neoplasms.

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

Study arms

• Experimental
  Dose-Finding Phase (Part 1): Rucaparib and Atezolizumab

  Approximately 6-18 participants with advanced gynecological cancers will receive different doses of rucaparib administered orally (PO) twice daily (BID) with a fixed dose of atezolizumab (1200 milligrams \[mg\] intravenously \[IV\], every 21 days) in 21-day cycles, starting with 400 mg rucaparib BID. The recommended Phase II dose (RP2D), determined by the highest dose level with an acceptable safety profile and with a minimum of 6 participants at which fewer than one-third of participants experience a DLT, was identified as 600 mg rucaparib twice a day (BID).

  Drug: Atezolizumab · Drug: Rucaparib

• Experimental
  Dose-Expansion Phase (Part 2): Rucaparib and Atezolizumab

  Two tumor-specific expansion cohorts will begin treatment with a 21-day run-in period of rucaparib monotherapy at the specified dose for rucaparib in the potential RP2D identified in Part 1 for the combination. Cohort 1 will have approximately 30 participants with advanced, platinum-sensitive ovarian cancer with tumors harboring a tBRCA mutation \[tBCRA(mut)\] or BRCA-like molecular signature \[tBRCA(wt)/LOH(high)\]. Cohort 2 will have approximately 20 participants with previously treated triple-negative breast cancer (TNBC) with a tBRCA mutation \[tBCRA(mut)\] or BRCA-like molecular signature \[tBRCA(wt)/LOH(high)\] and have not been exposed to cancer immunotherapies. Following the run in period, participants will receive the combination of rucaparib (specified dose, BID) and atezolizumab (1200 mg IV, every 21 days) in 21-day cycles.

  Drug: Atezolizumab · Drug: Rucaparib

Interventions

• DrugAtezolizumab

  Atezolizumab 1200 mg (equivalent to an average body weight-based dose of 15 milligrams per kilogram \[mg/kg\]) will be administered by IV infusion once every 3 weeks, corresponding to a 21-day treatment cycle. Participants will receive atezolizumab starting on Cycle 1, Day 1. Participants deriving clinical benefit will be allowed to continue on study treatment until the absence of unacceptable toxicity or compelling evidence of disease progression.

  Also known as: MPDL3280A; TECENTRIQ

• DrugRucaparib

  The starting dosage level of rucaparib for Part 1 is 400 mg PO BID during a 21-day treatment cycle. During Part 1, the rucaparib doses were increased up to a maximum of 600 mg PO BID using a standard 3 + 3 dose escalation. RP2D was identified as 600 mg BID. During Part 2 of the study, rucaparib will be dosed at the RP2D determined in Part 1. Participants in Part 1 of the study will receive rucaparib starting on Cycle 1, Day 1. During Part 2, participants will receive rucaparib monotherapy during a 21-day run-in period. After completion of the rucaparib run-in period and the first on-treatment biopsy between Days 15 and 21 of the run-in period, participants will begin Cycle 1, Day 1 of the rucaparib. Participants deriving clinical benefit will be allowed to continue on study treatment until the absence of unacceptable toxicity or compelling evidence of disease progression.

  Also known as: CO-338

Primary outcomes

1. Percentage of Participants With Adverse Events

   Time frame: Baseline up to approximately 45 months

2. Percentage of Participants With Dose-Limiting Toxicities (DLTs) [Part 1]

   Time frame: Cycle 1 (Day 1 up to Day 21)

3. Recommended Phase II Dose (RP2D) of Rucaparib for the Combination [Part 1]

   Time frame: Cycle 1 (Day 1 up to Day 21)

4. Number of Dose Modifications due to Adverse Events [Part 2]

   Time frame: Baseline up to approximately 45 months

Secondary outcomes

1. Percentage of Participants With Objective Response of Complete Response (CR) or Partial Response (PR) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

   Time frame: Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)

2. Percentage of Participants With Objective Response of CR or PR as Determined by Investigator Assessment Using Immune-Modified RECIST Incorporating Immune-Response (Cancer Antigen 125 [CA125] Response) Considerations

   Time frame: Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)

3. Duration of Response (DOR) as Determined by Investigator Assessment Using RECIST v1.1

   Time frame: Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)

4. DOR as Determined by Investigator Assessment Using Immune-Modified RECIST Incorporating Immune-Response (CA125 Response) Considerations

   Time frame: Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)

5. Progression-Free Survival (PFS) as Determined by Investigator Assessment Using RECIST v1.1

   Time frame: Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)

6. PFS as Determined by Investigator Assessment Using Immune-Modified RECIST Incorporating Immune-Response (CA125 Response) Considerations

   Time frame: Baseline until disease progression or death from any cause, whichever occurs first (assessed every 12 weeks up to approximately 45 months)

7. Overall Survival

   Time frame: Baseline until Death (up to 45 months)

8. Steady State Maximum Plasma Concentration Observed (Cmax) for Rucaparib [Part 1]

   Time frame: Predose (0 hours [hrs]) on Day 1 of Cycles 1-4; 0, 0.5, 1, 1.5, 2.5, 4, 6, 8 hrs postdose on Day 15 of Cycle 1; at 30 days after the last dose of study treatment (up to 45 months; cycle length=21 days)

9. Time to Maximum Plasma Concentration (tmax) for Rucaparib [Part 1]

   Time frame: Predose (0 hrs) on Day 1 of Cycles 1-4; 0, 0.5, 1, 1.5, 2.5, 4, 6, 8 hrs postdose on Day 15 of Cycle 1; at 30 days after the last dose of study treatment (up to 45 months; cycle length=21 days)

10. Area Under the Plasma Concentration-Time Curve (AUC) for Rucaparib [Part 1]

    Time frame: Predose (0 hrs) on Day 1 of Cycles 1-4; 0, 0.5, 1, 1.5, 2.5, 4, 6, 8 hrs postdose on Day 15 of Cycle 1; at 30 days after the last dose of study treatment (up to 45 months; cycle length=21 days)

11. Apparent Clearance (CL/F) for Rucaparib [Part 1]

    Time frame: Predose (0 hrs) on Day 1 of Cycles 1-4; 0, 0.5, 1, 1.5, 2.5, 4, 6, 8 hrs postdose on Day 15 of Cycle 1; at 30 days after the last dose of study treatment (up to 45 months; cycle length=21 days)

12. Minimum Plasma Concentration During the Dosing Interval (Cmin) for Rucaparib [Part 2]

    Time frame: Predose (0 hrs) on Day 1 of Cycles 1-4; at 30 days after the last dose of study treatment (up to 45 months; cycle length=21 days)

13. Serum Concentration of Atezolizumab [Parts 1 and 2]

    Time frame: Predose (0 hrs) on Day 1 of Cycles 1-4, 8 and every 8 cycles (up to 45 months); 0.5 hrs postdose (infusion duration=30-60 minutes) on Day 1 of Cycles 1 and 3; at 30 and 120 days after last dose of study treatment (up to 45 months; cycle length=21 days)

14. Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab

    Time frame: Baseline up to approximately 45 months