Pembrolizumab Activity in Patients With Homologous Recombination Competent and Deficient Tumors

NCT ID: NCT03274661

Last Updated: 2023-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 52 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-03
• Study Completion Date: 2022-03-19

Brief Summary

Phase II trial in which patients with metastatic solid tumors experiencing progression after first line standard chemotherapy or for which there is no standard chemotherapy, and for which pembrolizumab does not have an FDA or compendia listing approved indication, will receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.

Detailed Description

Patients with metastatic or recurrent solid malignancy who have progressed on first line standard of care treatment or for which defined standard of care does not exist or is not readily available are eligible to participate on this trial. Patients for which pembrolizumab has an FDA approved indication and for whom pembrolizumab is covered by their insurance should receive standard commercial pembrolizumab and will not be eligible for this trial.

The primary objective of this trial is to evaluate the Immune-Related Objective Response Rate (IR-ORR) achieved with pembrolizumab in patients with Fanconi Anemia Repair Pathway functionally competent and functionally deficient tumors.

Trial treatment should be administered on Day 1 of each cycle after all procedures/assessments have been completed. Trial treatment may be administered up to 3 days before or after the scheduled Day 1 of each cycle due to administrative reasons.

All trial treatments will be administered on an outpatient basis.

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. Target infusion timing is 30 minutes.

Expansion Cohort:

Ten (10) additional subjects with the diagnosis of metastatic or recurrent endometrial carcinoma will be enrolled in the trial at the conclusion of regular enrollment.

Conditions

Solid Tumor, Adult

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pembrolizumab 200 mg Q3W

Pembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle

Group Type: EXPERIMENTAL

Pembrolizumab 200 mg Q3W

Intervention Type: DRUG

Pembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle

Interventions

Pembrolizumab 200 mg Q3W

Pembrolizumab 200 mg Intravenous Infusion every 3 weeks administered on Day 1 of each 3 week cycle

Intervention Type: DRUG

Other Intervention Names

Pembrolizumab 200 mg

Eligibility Criteria

Inclusion Criteria

• Have measurable disease based on RECIST 1.1.
• Be willing to provide consent for retrieval of archival tumor material tissue from a previously obtained core or excisional biopsy of a tumor lesion.
• Have a tumor presentation at screening for which pembrolizumab does not have an FDA approved indication for commercial use.
• Have a performance status of 0, 1 or 2 on the ECOG Performance Scale.
• Demonstrate adequate organ function
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication.

Expansion cohort - additional criteria

1. Diagnosis of Endometrial Carcinoma or Sarcoma which is metastatic and has failed standard treatment or is recurrent, or for which standard chemotherapy is contraindicated or refused by patient.

2. Sufficient tissue is available for correlative studies

3. MSI studies have been performed, either by immunohistochemistry or next generation sequencing and results show that patient is MS low or stable.

Exclusion Criteria

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has a known history of active Bacillus Tuberculosis
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• 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).
• Has immunohistochemically proven mismatch repair deficient cancer
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Evidence of interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
• Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Miami Cancer Institute

OTHER

Sponsor Role: collaborator

Baptist Health South Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John P Diaz, MD

Role: PRINCIPAL_INVESTIGATOR

Miami Cancer Institute at Baptist Health, Inc.

Locations

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, United States

Countries

United States

References

Villalona-Calero MA, Diaz JP, Duan W, Diaz Z, Schroeder ED, Aparo S, Gatcliffe T, Albrecht F, Venkatappa S, Guardiola V, Garrido S, Rubens M, DeZarraga F, Vuong H. Pembrolizumab activity in patients with Fanconi anemia repair pathway competent and deficient tumors. Biomark Res. 2022 Jun 3;10(1):39. doi: 10.1186/s40364-022-00386-0.

Reference Type: RESULT

PMID: 35658948 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://baptisthealth.net/cancer-care/home

MCI - Website

Other Identifiers

MK-3475-663

Identifier Type: -

Identifier Source: org_study_id