Pembrolizumab Plus Olaparib in Patients With Recurrent Cervical Cancer

A Phase 2 Study of Pembrolizumab in Combination With Olaparib in Patients With Recurrent or Metastatic Cervical Cancer Who Had Disease Progression During or After Platinum-based Chemotherapy

This trial is a multicenter, single-arm, phase 2 study of pembrolizumab in combination with olaparib in recurrent or metastatic cervical cancer patients who had disease progression during or after platinum-based chemotherapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Olaparib

Detailed Description

This trial is a multicenter, single-arm, phase 2 study of pembrolizumab in combination with olaparib in recurrent or metastatic cervical cancer patients who had disease progression during or after platinum-based chemotherapy.

This study is planned to enroll 28 patients eligible for participation from multiple study sites in Japan.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Saitama
    • Hidaka, Saitama, Japan, 3501298
      • Saitama Medical Uiversity International Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Participants who are at least 20 years of age on the day of signing informed consent with histologically confirmed, recurrent or metastatic cervical cancer (squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma)
2. Participants with confirmed disease progression during or after platinum-based chemotherapy 1 or intolerant to or ineligible for platinum-based chemotherapy or ineligible participants
3. Participants with measurable disease based on RECIST 1.1 at screening
4. Participant is able to provide a core or excisional biopsy of a tumor lesion for testing of PD-L1 status, etc
5. Participants with Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1 upon the screening
6. Participants who may be expected to survive at least for 12 weeks after the first dose of study drug as determined by the principal investigator or a subinvestigator
7. Have adequate organ function

Exclusion Criteria:

1. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
2. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the enrollment.
3. Has received prior radiotherapy within 2 weeks prior to the enrollment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
4. Has received a live vaccine within 28 days prior to the enrollment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
5. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the enrollment.
6. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the enrollment.
7. Has a second malignancy advanced or requiring treatment within the past 3 years.The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, in situ cancers (e.g. in situ breast carcinomas).
8. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to the enrollment.
9. Has severe hypersensitivity (≥Grade 3) to the study drug and/or any of its excipients.
10. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and participants can be enrolled in the trial.
11. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
12. Has an active infection requiring systemic therapy.
13. Has a known history of Human Immunodeficiency Virus (HIV) infection.
14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
15. Has a known history of active TB (Bacillus Tuberculosis).
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
17. Participant has received colony-stimulating factors (eg, granulocyte colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 2 weeks prior to the enrollment.
18. Participant with clinically serious cardiovascular/cerebrovascular diseases including the following: cerebrovascular accident/stroke (less than 6 month prior to enrollment), myocardial infarction (less than 6 month prior to enrollment), unstable angina, congestive heart failure (the New York Heart Association (NYHA) Functional Classification Class 2 or severer), or serious arrhythmia. In addition, participants with history of bleeding tendency or recent major bleeding event in whom study drug administration carries higher risks as determined by the principal investigator will be excluded.
19. Participant who have acute or chronic disease with severe and/or clinical symptoms which may compromise the tolerance to this study or competence to consistently follow the study procedures as determined by the principal investigator
20. Participants with medical history of receiving all the PARP inhibitors
21. Participant is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued before the study drug initiation. The required washout period prior to starting olaparib is 2 weeks.
22. Participant is currently receiving either strong (eg, phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine, and St John's Wort) or moderate (eg. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued before the study drug initiation. The required washout period prior to starting olaparib is 5 weeks for phenobarbital and 3 weeks for other agents.
23. Participant is either unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption).
24. Participant has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg, unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances, etc.), or participant has congenital long QT syndrome.
25. Has a major surgery history 4 weeks prior to the enrollment (e.g.: diagnostic biopsy is not regarded as the major surgery)
26. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
27. Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit within 120 days after the last dose of trial treatment.
28. Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.
29. Participant has had an allogenic tissue/solid organ transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pembrolizumab plus olaparib; Until RECIST-based confirmation of progressive disease (PD), death, manifestation of intolerable toxicity, or participant withdrawal from the study, study participants will continue intravenous infusion of pembrolizumab 200 mg every three weeks (Q3W) in combination with oral olaparib 300 mg twice daily (BID) (combination therapy)	Drug: Pembrolizumab; pembrolizumab 200 mg every three weeks (Q3W); Other Names: KEYTRUDA; Drug: Olaparib; olaparib 300 mg twice daily (BID); Other Names: LYNPARZA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective Response Rate (ORR) will be evaluated after pembrolizumab in combination with olaparib based on RECIST 1.1.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate on iRECIST	To assess ORR after administration of pembrolizumab in combination with olaparib based on iRECIST.	3 years
Duration of response	To assess duration of response (DOR) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1 and iRECIST.	3 years
Durable response rate	To assess durable response rate (DRR) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1 and iRECIST	3 years
Percentage of patients with response to administration of pembrolizumab in combination with olaparib for 6 months and longer	To assess the percentage of patients with response to administration of pembrolizumab in combination with olaparib for 6 months and longer based on RECIST 1.1 and iRECIST	3 years
PFS after administration of pembrolizumab in combination with olaparib	To assess progression-free survival (PFS) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1 and iRECIST	3 years
Incidence of treatment-related adverse events after administration of pembrolizumab in combination with olaparib	To assess the number of participants with treatment-related adverse events after administration of pembrolizumab in combination with olaparib based on CTCAE v5.0	3 years
Objective Response Rate based on PD-L1 status	ORR will be evaluated after pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.	3 years
Duration of response based on PD-L1 status	To assess DOR after administration of pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.	3 years
Durable response rate based on PD-L1 status	To assess DRR after administration of pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.	3 years
PFS based on PD-L1 status	To assess PFS after administration of pembrolizumab in combination with olaparib stratified by PD-L1 status based on RECIST 1.1 and iRECIST.	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival after administration of pembrolizumab in combination with olaparib based on RECIST 1.1	To assess overall survival (OS) after administration of pembrolizumab in combination with olaparib based on RECIST 1.1	3 years

Collaborators and Investigators

• Sponsor: Saitama Medical University International Medical Center
• Collaborators: National Cancer Center, Japan; Tokyo University; Cancer Institute Hospital, Japan; Aichi Cancer Center
• Investigators: Principal Investigator: Kosei Hasegawa, MD, PhD, Saitama Medical University International Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: November 2, 2020
• First Submitted That Met QC Criteria: November 22, 2020
• First Posted (Actual): November 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 9, 2022
• Last Update Submitted That Met QC Criteria: August 8, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: olaparib; pembrolizumab; cervical cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib; Pembrolizumab
• Other Study ID Numbers: GOTIC-025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes