Pembrolizumab and Olaparib in Cervical Cancer Patients

NCT04483544 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 2019-JEK-DIA-001
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

The study is a non-randomized, open-label phase II clinical trial to test the investigational combination of the drug pembrolizumab with the drug olaparib in patients diagnosed with advanced or recurrent cervical carcinoma after standard chemotherapy.

Conditions

Cervical Cancer; Cervical Carcinoma

Outcome Measures

Primary Outcomes (1)

• Immune Overall Response Rate

  Overall objective Response Rate by Immune Response Evaluation Criteria in Solid Tumors (iRECIST) criteria (iORR)

  3 years

Secondary Outcomes (4)

• Progression Free Survival

  3 years

• Number of Patient Reporting Treatment-emergent Adverse Events (TEAEs)

  3 years

• Number of Patients With Baseline Tumor Deficiencies

  baseline

• Duration of Response

  3 years

Study Arms (1)

Treatment

EXPERIMENTAL

PD-1 inhibitor pembrolizumab, in combination with the PARP inhibitor olaparib

Drug: pembrolizumab; Drug: olaparib

Interventions

pembrolizumab DRUG

PD-1 inhibitor pembrolizumab, 200mg intravenously (IV) every 3 weeks

Treatment

olaparib DRUG

PARP inhibitor olaparib 300 mg orally, twice daily (BID)

Treatment

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Cervical cancer is a disease of the female genital tract. No male patients will be enrolled.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of cervical carcinoma will be enrolled in this study.
• Cervical cancer is a disease of the female genital tract. No male patients will be enrolled.
• A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment.
• Participant must have recurrent cervical cancer and have a low potential for cure with radiation therapy or surgery alone and:
• a. May have received up to 2 prior chemotherapy regimens. Platinum sensitizing agents for radiation therapy are considered a chemotherapy regimen.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and this protocol.
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed prior to the first dose of treatment.
• Patient's life expectancy ≥ 16 weeks.
• Have adequate organ function as defined in the following table (Table 1). Specimens must be collected within 10 days prior to the start of study treatment. Before patients can be enrolled, they must have normal laboratory values as outlined in Table 1. Labs must also fall within normal limits prior to infusion.

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to the first dose of treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
• 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).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to the first dose of treatment.
• Has received prior radiotherapy within 2 weeks of start of study intervention. 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.
• Has received a live vaccine within 30 days prior to the first dose of study drug. 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.
• 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 first dose of study intervention.
• Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
• Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
• 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 first dose of study drug.
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma.
• 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 first dose of study intervention.
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients, or patients with a known hypersensitivity to olaparib or any of the excipients of the product.

Sponsors & Collaborators

• Baptist Health South Florida: lead
• Florida Department of Health: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Miami Cancer Institute at Plantation

Plantation, Florida, 33324, United States

Location

Related Links

• Miami Cancer Institute

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

pembrolizumab; olaparib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Limitations and Caveats

The rapidly evolving field of immunotherapy in cervical cancer moved pembrolizumab to the frontline setting, which made it difficult to recruit eligible participants. The study was terminated early, and statistical analysis could not be completed with the small number accrued. The planned FATSI analysis and correlative studies also were not completed due the collaborating laboratory's closure. With the early termination, a new laboratory was not sought.

Results Point of Contact

• Title: Director, Research Concept & Protocol Development
• Organization: Miami Cancer Institute at Baptist Health, Inc.

MCIResearchConceptAndProtocolDev@baptisthealth.net

(786) 527-9546

Study Officials

• John P. Diaz, MD

  Miami Cancer Institute at Baptist Health Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: PD-1 inhibitor pembrolizumab, in combination with the PARP inhibitor olaparib

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 23, 2020
• Study Start: December 3, 2020
• Primary Completion: December 12, 2024
• Study Completion: December 12, 2024
• Last Updated: April 29, 2025
• Results First Posted: April 29, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)