A Study in Ovarian Cancer Patients Evaluating Rucaparib and Nivolumab as Maintenance Treatment Following Response to Front-Line Platinum-Based Chemotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

pharmaand GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Nov 2018 → ongoing

Decision date (initial)

2024-11-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bristol-Myers Squibb Co.

External identifiers

EU CT number

2024-516662-11-00

EudraCT number

2017-004557-17

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacoeconomic, Pharmacokinetic, Safety, Efficacy, Pharmacogenetic

To evaluate PFS by Response Evaluation Criteria in Solid Tumors (RECIST), as
assessed by the investigator (invPFS) using the following separate comparisons:
- Monotherapy: Arm B (oral rucaparib + intravenous [IV] placebo) vs Arm D
(placebo [oral and IV]) in the HRD and intent-to-treat (ITT) sub/populations
- Combination: Arm A (oral rucaparib + IV nivolumab) vs Arm B (oral rucaparib
+ IV placebo) in the ITT Population

Secondary objectives 1

1. To evaluate PFS by RECIST, as assessed by blinded independent central review (BICR; bicrPFS) • To evaluate survival benefit • To evaluate the objective response rate (ORR) and duration of response (DOR), as assessed by the investigator, in patients with measurable disease at baseline • To evaluate safety

Conditions and MedDRA coding

Ovarian epithelial cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Eligible patients must meet the following inclusion criteria: 1. Have signed an Institutional Review Board (IRB)/ Independent Ethics Committee (IEC)-approved informed consent form (ICF) prior to any study-specific evaluation.
2. 2. Be ≥ 18 years of age at the time the ICF is signed (patients enrolled in South Korea, Taiwan, and Japan must be ≥ 20 years of age at the time the ICF is signed).a. Patients enrolled in the open-label safety cohort in Japan must be of Japanese ethnicity (ie, both parents are native Japanese and were born in Japan)
3. 3. Have newly diagnosed, histologically confirmed, advanced (International Federation of Gynecology and Obstetrics [FIGO] stage III-IV), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer.
4. 4. Completed cytoreductive surgery, including at least a bilateral salpingo-oophorectomy and partial omentectomy, either prior to chemotherapy (primary surgery) or following neoadjuvant chemotherapy (interval debulking).
5. 5. Have received 4 to 8 cycles of first-line platinum-doublet treatment per standard clinical practice, including a minimum of 4 cycles of a platinum/ taxane combination. a. A patient with best response of partial response (PR) must have received at least 6 cycles. b. Bevacizumab is allowed during the chemotherapy phase, but not during maintenance ie, during therapy directed by this protocol.
6. 6. Have completed first-line platinum-based chemotherapy and surgery with a response, in the opinion of the investigator, defined as no evidence of disease progression radiologically or through rising CA-125 (per Gynecologic Cancer Intergroup [GCIG] guidelines) at any time during front-line treatment; and: a. No evidence of measurable disease by RECIST v1.1 (if complete resection/R0 at b. primary or interval cytoreductive surgery); or c. b. A partial or complete response per RECIST v1.1 (if measurable disease was present d. after surgery and prior to chemotherapy); or e. c. A GCIG CA-125 response (if only non-measurable disease was present after surgery f. and prior to chemotherapy). g. 7. Pre-treatment CA-125 measurements must meet criterion specified below: h. If the first value is within upper limit of normal (ULN), the patient is eligible to be i. randomized and a second sample is not required; j. If the first value is greater than ULN, a second assessment must be performed at k. least 7 days after the first. If the second assessment is ≥ 15% than the first value, the l. patient is not eligible. m. 8. Patient must be randomized within 8 weeks of the first day of the last cycle of n. chemotherapy. 9. Have sufficient formalin-fixed paraffin-embedded (FFPE) tumor tissue (1 × 4 μm o. section for hematoxylin and eosin [H&E] stain and approximately 8 to 12 × 10 μm p. sections, or equivalent) available for planned analyses. q. a. Submission of a tumor block is preferred; if sections are provided, these must all be r. from the same tumor sample. s. b. Tumor tissue from the cytoreductive surgery is required. t. c. Sample must be received at the central laboratory at least 3 weeks prior to planned u. start of treatment to enable stratification for randomization. v. 10. Have adequate organ function confirmed by the following laboratory values obtained w. within 14 days prior to randomization: x. a. Bone Marrow Function y. i. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L z. ii. Platelets ≥ 100 × 109/L aa. iii. Hemoglobin ≥ 9 g/dL bb. b. Hepatic Function cc. i. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) dd. ≤ 1.5 × ULN ee. ii. Bilirubin ≤ 1.5 × ULN; < 2 × ULN if hyperbilirubinemia is due to Gilbert's ff. syndrome gg. iii. Serum albumin ≥ 30 g/L (3.0 g/dL) hh. c. Renal Function ii. i. Serum creatinine ≤ 1.5 × ULN unless estimated glomerular filtration rate (GFR) jj. ≥ 30 mL/min using the Cockcroft Gault formula kk. 11. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
7. 7. Pre-treatment CA-125 measurements must meet criterion specified below: h. If the first value is within upper limit of normal (ULN), the patient is eligible to be i. randomized and a second sample is not required; j. If the first value is greater than ULN, a second assessment must be performed at k. least 7 days after the first. If the second assessment is ≥ 15% than the first value, the l. patient is not eligible.
8. 8. Patient must be randomized within 8 weeks of the first day of the last cycle of n. chemotherapy.
9. 9. Have sufficient formalin-fixed paraffin-embedded (FFPE) tumor tissue (1 × 4 μm section for hematoxylin and eosin [H&E] stain and approximately 8 to 12 × 10 μm sections, or equivalent) available for planned analyses. a. Submission of a tumor block is preferred; if sections are provided, these must all be from the same tumor sample. b. Tumor tissue from the cytoreductive surgery is required. c. Sample must be received at the central laboratory at least 3 weeks prior to planned start of treatment to enable stratification for randomization.
10. 10. Have adequate organ function confirmed by the following laboratory values obtained within 14 days prior to randomization: a. Bone Marrow Function y. i. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L z. ii. Platelets ≥ 100 × 109/L aa. iii. Hemoglobin ≥ 9 g/dL bb. b. Hepatic Function cc. i. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) dd. ≤ 1.5 × ULN ee. ii. Bilirubin ≤ 1.5 × ULN; < 2 × ULN if hyperbilirubinemia is due to Gilbert's ff. syndrome gg. iii. Serum albumin ≥ 30 g/L (3.0 g/dL) hh. c. Renal Function ii. i. Serum creatinine ≤ 1.5 × ULN unless estimated glomerular filtration rate (GFR) jj. ≥ 30 mL/min using the Cockcroft Gault formula
11. 11. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

Exclusion criteria 16

1. Patients will be excluded from participation if any of the following criteria apply: 1. Non-epithelial tumors (pure sarcomas) or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors. Mixed mullerian tumors/carcinosarcomas are allowed.
2. 2. Active second malignancy, ie, patient known to have potentially fatal cancer present for which she may be (but not necessarily) currently receiving treatment. a. Patients with a history of malignancy that has been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or patients with surgically-cured low-risk tumors, such as early-stage cervical or endometrial cancer are allowed to enroll.
3. 3. Known central nervous system brain metastases.
4. 4. Any prior treatment for ovarian cancer, other than the first-line platinum regimen, including any maintenance treatment between completion of the platinum regimen and initiation of study drug in this study. a. Ongoing hormonal treatment for previously treated breast cancer is permitted. Hormonal maintenance treatment for ovarian cancer is not allowed
5. 5. Has evidence of interstitial lung disease, active pneumonitis, myocarditis, or a history of myocarditis.
6. 6. Patients with an active, known or suspected autoimmune disease (eg, autoimmune hepatitis). Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
7. 7. Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
8. 8. Drainage of ascites during the final 2 cycles of treatment with the platinum regimen.
9. 9. Pre-existing duodenal stent and/or any gastrointestinal disorder or defect that would, in the opinion of the investigator, interfere with absorption of study treatment.
10. 10. Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: Testing for HIV must be performed at all sites where mandated locally.
11. 11. Any positive test result for hepatitis B and/or known history of hepatitis B infection including patients with undetectable hepatitis B virus (HBV) DNA and inactive carriers; positive test result for hepatitis C antibody (anti-HCV; except if HCV-RNA negative).
12. 12. Pregnant, or breast feeding. All study participants must agree to avoid pregnancy achieved through assisted reproductive technology for the duration of study treatment and for a minimum of 6 months following the last dose of study drug (oral or IV, whichever is later).
13. 13. Received chemotherapy within 14 days prior to first dose of study drug and/or ongoing adverse effects from such treatment > National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 1, with the exception of Grade 2 non-hematologic toxicity such as alopecia, peripheral neuropathy, Grade 2 anemia with hemoglobin ≥ 9 g/dL, and related effects of prior chemotherapy that are unlikely to be exacerbated by treatment with study drug.
14. 14. Non-study related minor surgical procedure (eg, placement of a central venous access port) ≤ 5 days, or major surgical procedure ≤ 21 days, prior to first dose of study drug; in all cases, the patient must be sufficiently recovered and stable before treatment administration.
15. 15. Presence of any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results, and, in the opinion of the investigator, would make the patient inappropriate for entry into the study.
16. 16. Hospitalization for bowel obstruction within 12 weeks prior to enrollment. No waivers of these inclusion or exclusion criteria will be granted by the investigator and the sponsor or its designee for any patient randomized into the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint for the study is investigator-determined progression-free survival (PFS) by RECIST v1.1. Investigator-determined PFS is defined as the time from randomization to disease progression, according to RECIST v1.1 criteria as assessed by the investigator, or death due to any cause, whichever occurs first.

Secondary endpoints 4

1. Secondary Efficacy Endpoints: Progression-free survival (PFS) as assessed by blinded independent central review (BICR) by RECIST will be tested as a stand-alone secondary endpoint, outside of the step-down procedure for multiplicity adjustment, due to it being supportive of the primary endpoint.
2. BicrPFS is defined as the time from randomization to disease progression, according to RECIST v1.1 criteria as assessed by BICR, or death due to any cause, whichever occurs first. Only tumor scans prior to start of any subsequent anti-cancer treatment are included. Overall survival is defined as the time from randomization to death due to any cause.
3. Analyses of objective response rate (ORR) will be performed in the subgroup of patients with measurable disease at baseline and will be summarized with frequencies and percentages. Duration of response (DOR) will be tested as a stand-alone secondary endpoint, outside of the step-down procedure for multiplicity adjustment.
4. DOR is defined as the interval from the first documentation of objective response (RECIST v1.1) to the earlier of the first documentation of disease progression (per RECIST v1.1) or death from any cause. Safety Analysis: Adverse events, clinical laboratory results, vital signs, ECOG performance status, body weight, and concomitant medications/procedures.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

pharmaand GmbH

Sponsor organisation

pharmaand GmbH

Address

Taborstrasse 1

City

Vienna

Postcode

1020

Country

Austria

Scientific contact point

Organisation

pharmaand GmbH

Contact name

Medical information

Public contact point

Organisation

pharmaand GmbH

Contact name

Medical information

Third parties 7

Locations

11 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 78 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications