Pembrolizumab for the Treatment of Relapsed or Refractory Multiple Myeloma After Anti-BCMA CAR-T Therapies

NCT05191472 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 212530NCI-2021-13897
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests whether pembrolizumab works to shrink tumors in patients with multiple myeloma whose cancer has come back (relapsed) or did not respond to previous treatment (refractory) with anti-BCMA CAR-T therapies. Immunotherapy with pembrolizumab, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread.

Conditions

Multiple Myeloma; Multiple Myeloma in Relapse; Multiple Myeloma, Refractory; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma

Keywords

CAR-T

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The International Myeloma Working Group (IMWG) uniform response criteria will be used to assess disease response and progression. The response rate is defined as the proportion of patients achieving a partial response (PR), very good partial response (VGPR), complete response (CR), or a stringent complete response (sCR) after 4 cycles of pembrolizumab therapy. A 95% confidence interval will also be reported.

  Up to 4 cycles (1 cycle is equal to 21 days)

Secondary Outcomes (10)

• Proportion of Participants With Reported Treatment-related Adverse Events

  Up to 30 days after discontinuing study treatment, approximately 1 year and 8 months

• Proportion of Participants With Cytokine Release Syndrome (CRS)

  Up to 30 days after discontinuing study treatment, approximately 1 year and 8 months

• Proportion of Participants With Immune-effector Cell-associated Neurotoxicity Syndrome (ICANS)

  Up to 30 days after discontinuing study treatment, approximately 1 year and 8 months

• Proportion of Participants Discontinuing Treatment Due to Toxicity

  Up to 30 days after discontinuing study treatment, approximately 1 year and 8 months

• Proportion of Participants by Best Achieved Response Rate

  Approximately 1 year and 8 months

Study Arms (1)

Treatment (pembrolizumab)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Biological: Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475

Treatment (pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Male/female participants who are 18 years of age or older on the day of signing informed consent with histologically confirmed diagnosis of multiple myeloma will be enrolled in this study.
• Ability to understand a written informed consent document, and the willingness to sign it or a legally acceptable representative (if applicable).
• Have an Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky \> 60%). Evaluation of ECOG is to be performed within 7 days prior to the start of study treatment.
• The effects of pembrolizumab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception for the duration of study participation and 120 days after last administration of study treatment.
• Female participants are eligible if not pregnant, not breastfeeding, and one of the following:
• Not a woman of childbearing potential (WOCBP) OR
• WOCBP who agrees to follow contraceptive guidance during treatment period and at least 120 days following last dose of study treatment.
• Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 120 days after last administration of study treatment. Men should also refrain from donating sperm during this period.
• Participants must have either
• progressive disease after prior anti-BCMA CAR-T therapy and have not started another systemic anti-cancer therapy following progression after anti-BCMA CAR-T therapy. Patients who received localized radiotherapy alone for symptomatic relief of progressive disease following anti-BCMA CAR-T will be allowed.
• b. stable disease as best hematologic response after at least 30 days post anti-BCMA CAR-T infusion.
• Progression after anti-BCMA CAR-T is defined by International Myeloma Working Group (IMWG) criteria:
• Increase of \> 25% from lowest response value in any one or more of the following:
• Serum M-component and/or (the absolute increase must be \> 0.5 g/dL).

You may not qualify if:

• A WOCBP who has a positive urine pregnancy test within 72 hours prior to study treatment initiation. 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-programmed cell death protein 1 (anti PD-1), anti-programmed death-ligand 1 (anti PD-L1), or anti programmed cell death 1 ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX 40, Cluster of Differentiation 137 (CD137)).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study treatment initiation.
• Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to =\< grade 1 or baseline. Participants with =\< grade 2 neuropathy may be eligible.
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received anti-BCMA CAR-T infusion \< 30 days prior to study treatment initiation.
• Has received subsequent systemic anti-cancer therapy following anti-BCMA CAR-T therapy. Participants who received localized radiotherapy alone for symptom control following anti-BCMA CAR-T therapy will be allowed to participate.
• 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-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are generally Messenger RNA (mRNA)-based or viral vector vaccines (replication-incompetent) and are 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.
• \* Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
• Has a diagnosis of primary 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 an active history of a second malignancy requiring treatment, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Participants with the following low-risk or non-invasive malignancies will be allowed:
• Basal cell carcinoma of the skin.
• Squamous cell carcinoma of the skin.

Sponsors & Collaborators

• Alfred Chung, MD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

The study closed earlier than expected due to slow accrual

Results Point of Contact

• Title: Dr. Alfred Chung, MD
• Organization: University of California, San Francisco

Alfred.Chung@ucsf.edu

(415) 476-1000

Study Officials

• Alfred Chung, MD

  University of California, San Francisco

  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 INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 2, 2022
• First Posted: January 13, 2022
• Study Start: May 3, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: January 15, 2025
• Results First Posted: January 15, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)