Pembrolizumab Activity in Patients With Homologous Recombination Competent and Deficient Tumors

NCT03274661 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: MK-3475-663
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumor, Adult

Keywords

solid tumor, Pembrolizumab,

Outcome Measures

Primary Outcomes (1)

• Immune-related Objective Response Rate

  Immune-related Response Criteria (irRC) will be utilized for assessment of response to therapy, defined as the percent of participants who achieved complete or partial response. Per irRC, for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all lesions in two consecutive observations not less than 4 weeks apart; Partial Response (PR), ≥50% decrease in tumor burden compared with baseline in two observations at least 4 weeks apart.

  20 weeks

Secondary Outcomes (2)

• Progression-free Survival (PFS)

  20 weeks

• Overall Response

  3 years

Study Arms (1)

Pembrolizumab 200 mg Q3W

EXPERIMENTAL

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

Drug: Pembrolizumab 200 mg Q3W

Interventions

Pembrolizumab 200 mg Q3W DRUG

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

Also known as: Pembrolizumab 200 mg

Pembrolizumab 200 mg Q3W

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• Sufficient tissue is available for correlative studies
• MSI studies have been performed, either by immunohistochemistry or next generation sequencing and results show that patient is MS low or stable.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Baptist Health South Florida: lead
• Merck Sharp & Dohme LLC: collaborator
• Miami Cancer Institute: collaborator

Study Sites (1)

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176, United States

Location

Related Publications (1)

• 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.

  PMID: 35658948 RESULT

Related Links

• MCI - Website

MeSH Terms

Interventions

pembrolizumab

Results Point of Contact

• Title: Dr. John Diaz, Principal Investigator
• Organization: Miami Cancer Institute at Baptist Health, Inc.

johnpd@baptisthealth.net

(786) 527-8284

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: Eligible participants will receive pembrolizumab intravenously at a dose of 200 mg every 3 weeks.

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 7, 2017
• Study Start: November 3, 2017
• Primary Completion: October 20, 2020
• Study Completion: March 19, 2022
• Last Updated: October 19, 2023
• Results First Posted: October 19, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)