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BMS-986504 in Combination With Pemetrexed for the Treatment of Metastatic Solid Tumors With MTAP Deletion

ConditionsMetastatic Biliary Tract CarcinomaMetastatic Colon CarcinomaMetastatic Esophageal CarcinomaMetastatic Malignant Digestive System NeoplasmMetastatic Malignant Solid NeoplasmMetastatic Pancreatic CarcinomaStage IV Colon Cancer AJCC v8Stage IV Pancreatic Cancer AJCC v8
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorNorthwestern University

About this trial

This phase Ib/II trial tests the safety and side effects of BMS-986504 in combination with pemetrexed and how well the combination works in treating patients with solid tumors with MTAP deletion and that has spread from where it first started (primary site) to other places in the body (metastatic). The MTAP gene helps cells recycle important parts needed to make deoxyribonucleic acid (DNA), which is needed for cell growth and function. MTAP deletion means that the MTAP gene is missing. BMS-986504, a PRMT5 inhibitor, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make DNA and may kill tumor cells. Giving BMS-986504 in combination with pemetrexed may be safe, tolerable, and/or effective in treating patients with metastatic solid tumors with MTAP deletion.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Patients must have pathologically or cytologically confirmed metastatic solid tumor of gastrointestinal origin with MTAP deletion including pancreatic cancer, biliary cancer, esophageal cancer and colon cancer (Cohort A) or other metastatic solid malignancy with MTAP deletion (Cohort B) confirmed by validated next generation sequencing tissue techniques only

NOTE: Both internal and external validated next generation sequencing (NGS) panels are acceptable

Progressive disease (PD) after one previous standard of care line of treatment

NOTE: symptoms from clinical evaluation for PD will be sufficient

Disqualifiers

Patients who received prior pemetrexed containing chemotherapy (apart from NSCLC)

Patients with prior treatment with a PRMT5 or MAT2A inhibitor therapy

Patients with pre-existing clinically significant interstitial lung disease (ILD)

Patients who have had chemotherapy or radiotherapy ≤ 21 days prior to planned treatment start date.

Trial design

Design model

Single group

Treatments tested in this trial

  • Biospecimen Collection

    Procedure/Surgery

    Undergo blood sample collection

  • Computed Tomography

    Procedure/Surgery

    Undergo CT

  • Pemetrexed

    Drug

    Given IV

  • PRMT5 Inhibitor BMS-986504

    Drug

    Given PO

Treatment groups

72 Participants
are divided into 1 treatment group
Group A: Treatment (BMS-986504, pemetrexed)Experimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Dose limiting toxicity

Will be summarized descriptively by frequency and grade using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

Time frame
Up to 21 days
2

Incidence of treatment-emergent adverse events (AEs)

Will be summarized descriptively by frequency and grade using the NCI CTCAE v 5.0. Will be tabulated by system organ class and preferred term.

Time frame
Up to 30 days after last dose of study treatment
3

Incidence of serious AEs

Will be summarized descriptively by frequency and grade using the NCI CTCAE v 5.0.

Time frame
Up to 30 days after last dose of study treatment
4

Incidence of grade 3 or greater adverse events

Will be summarized descriptively by frequency and grade using the NCI CTCAE v 5.0.

Time frame
Up to 30 days after last dose of study treatment

Secondary outcomes

1

Objective response rate

Will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. Will be defined as the overall percentage of patients with complete response (CR) plus partial response (PR). Point estimates and corresponding two-sided 95% exact (Clopper-Pearson) confidence intervals will be reported. Will be compared against the null hypothesis rate of 15% using a one-sided binomial test consistent with the Simon's two-stage design framework.

Time frame
From baseline until disease progression, initiation of subsequent anti-cancer therapy, or completes study participation, whichever occurs first, assessed up to 12 months
2

Duration of response (DOR)

Disease progression will be defined as experiencing progressive disease per RECIST v 1.1 or death due to disease. Will be analyzed using the Kaplan-Meier method, with censoring at the date of the last tumor assessment prior to progression or death. Median DOR and corresponding 95% confidence intervals will be reported.

Time frame
From the day when CR or PR is first observed until the earlier of the day of first documented disease progression or death from any cause, assessed up to 12 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Northwestern University

Lead sponsor

National Cancer Institute (NCI)

Collaborator

Source ClinicalTrials.gov
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