Pembrolizumab/placebo plus paclitaxel with or without bevacizumab for platinum-resistant recurrent ovarian cancer.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Oct 2021 → ongoing

Decision date (initial)

2023-08-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-506177-35-00

EudraCT number

2020-005027-37

WHO UTN

U1111-1287-5318

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenetic, Efficacy, Pharmacokinetic, Pharmacogenomic

To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to progression-free survival (PFS) per RECIST 1.1 as assessed by the investigator.

Secondary objectives 4

1. To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab with respect to overall survival (OS).
2. To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab with respect to PFS per RECIST 1.1 by blinded independent central review (BICR) for PD-L1+ (CPS ≥1) and all participants.
3. To evaluate safety and tolerability of pembrolizumab plus paclitaxel with or without bevacizumab.
4. To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to Global Health Status/Quality of Life (GHS/QoL) score using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and abdominal/gastrointestinal (GI) symptoms using EORTC Ovarian Cancer-Specific Quality of Life Questionnaire (QLQ-OV28) for PD-L1+ (CPS ≥1) and all participants.

Conditions and MedDRA coding

Ovarian, fallopian tube, or primary peritoneal carcinoma.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Has histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
2. Has received 1 or 2 prior lines of systemic therapy for ovarian cancer (OC), including at least 1 prior platinum-based therapy. Participants may have received a prior poly (ADP-ribose) polymerase inhibitor (PARPi), anti-PD-1/anti-PD-L1 therapy, bevacizumab, or hormonal therapy; these will not be considered a separate line of therapy. Any chemotherapy regimen change due to toxicity in the absence of disease progression will be considered part of the same line of therapy.
3. Has provided documented informed consent for the study.
4. Has radiographic evidence of disease progression within 6 months (180 days) after the last dose of platinum-based chemotherapy for OC (i.e., platinum-resistant disease).
5. Is a candidate for paclitaxel chemotherapy (and bevacizumab, if using).
6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 3 days before randomization.
7. For a female participant, she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and uses a contraceptive method that is highly effective (with a failure rate of <1% per year).
8. Has radiographically evaluable disease, either measurable or nonmeasurable per RECIST 1.1, as assessed by the local site investigator.
9. Archival tumor tissue sample or newly obtained core or incisional/excisional biopsy of a tumor lesion not previously irradiated has been provided.
10. Have adequate organ function.

Exclusion criteria 24

1. Has nonepithelial cancers, borderline tumors, mucinous, seromucinous that is predominantly mucinous, malignant Brenner’s tumor and undifferentiated carcinoma.
2. Has primary platinum-refractory disease, defined as disease that has progressed per radiographic imaging while receiving or within 28 days of the last dose of first-line platinum-based therapy.
3. Has prior disease progression on weekly paclitaxel alone.
4. Has received >2 prior lines of systemic therapy for OC.
5. Has received prior systemic anticancer therapy including investigational agents or maintenance therapy (including bevacizumab maintenance therapy), within 4 weeks before randomization.
6. Has received prior radiation therapy within 2 weeks of start of study intervention.
7. Has not recovered adequately from surgery and/or any complications from the surgery.
8. Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor,[GM-CSF] or recombinant erythropoietin) within 4 weeks before randomization.
9. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
10. Has received investigational agent or has used an investigational device within 4 weeks prior to study intervention.
11. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
12. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
13. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
14. Has severe hypersensitivity (≥Grade 3) to pembrolizumab, paclitaxel, or bevacizumab (if using) and/or any of their excipients.
15. Has an active autoimmune disease that has required systemic treatment in the past 2 years.
16. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
17. Has an active infection requiring systemic therapy.
18. Has a known history of human immunodeficiency virus (HIV) infection.
19. Has a known history of Hepatitis B or known active Hepatitis C virus infection.
20. Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study.
21. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
22. Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.
23. Has had an allogenic tissue/solid organ transplant.
24. For bevacizumab treatment - Has uncontrolled hypertension. - Has current, clinically relevant bowel obstruction including related to underlying epithelial OC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam. - Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active gastrointestinal bleeding within 6 months before randomization.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Investigator.

Secondary endpoints 8

1. Overall Survival (OS).
2. PFS per RECIST 1.1 by Blinded Independent Central Review (BICR).
3. Number of Participants who Experience an Adverse Event (AE).
4. Number of Participants who Discontinue Study Treatment due to an AE.
5. Change From Baseline in Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
6. Time to Deterioration (TTD) in the GHS/Qol Score (Items 29 and 30) Using the EORTC QLQ-C30.
7. Change From Baseline in the Abdominal and Gastrointestinal (GI) Symptoms Score (Items 31 to 36) Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale.
8. TTD in the Abdominal and GI Symptoms Score (Items 31 to 36) Using the EORTC QLQ-OV28 Abdominal/GI Symptom Scale.

Investigational products

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

Test 1

Placebo 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Agata Bogusz

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Agata Bogusz

Third parties 7

Locations

10 EU/EEA countries · 33 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 71 files

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

Application history

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