Solid Tumors
Conditions
Keywords
MTAP, CDKN2A, PRMT5, MountainTAP, Targeted therapy, Brain cancer, GBM, Melanoma, NSCLC, Lung cancer PDAC, Pancreatic cancer, Navlimetostat, Navli
Brief summary
This is an open-label, multicenter Phase 2 study evaluating BMS-986504 in participants with advanced and/or metastatic solid tumors that have MTAP deletion. The study includes a monotherapy component and a combination component in which BMS-986504 is given with other anti-cancer agents. The trial will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of BMS-986504 alone and in combination regimens.
Detailed description
Part 1 will include parallel enrolment of tumor-specific dose-expansion cohorts evaluating BMS-986504 as monotherapy. Part 2 will include dose-escalation cohorts in which BMS-986504 is given in combination with other anticancer agents. Additional cohorts may be added based on emerging data.
Interventions
DRUGBMS-986504
Specified dose on specified days
DRUGDaraxonrasib
Specified dose on specified days
Specified dose on specified days
DRUGTemozolomide
Specified dose on specified days
DRUGPumitamig
Specified dose on specified days
DRUGPemetrexed
Specified dose on specified days
DRUGCarboplatin
Specified dose on specified days
DRUGNab-paclitaxel
Specified dose on specified days
DRUGGemcitabine
Specified dose on specified days
DRUGPaclitaxel
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must have histologically confirmed diagnosis of advanced and/or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene detected in tumor tissue. * Depending on the cohort enrolled, participants must have received standard therapies appropriate for their tumor type and stage with disease progression on or after the most recent treatment (there must be no available treatment with curative intent or participant is ineligible or declines treatment) or be treatment-naïve with no prior systemic anticancer therapy for their unresectable or metastatic disease. * Participant must have presence of at least one measurable tumor lesion per RECIST v1.1 or mRECIST at baseline. * Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) should be ≤ 1.5 × ULN; subjects with liver metastasis or liver cancer should be ≤ 2 × ULN. * Participant must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion criteria
* Participants must not have prior treatment with a PRMT5 or Methionine adenosyl transferase 2A (MAT2A) inhibitor. * Participants must not have active brain metastases or carcinomatous meningitis. Participants are eligible if brain metastases are adequately treated, and participants are neurologically stable for at least 2 weeks prior to enrollment without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent). * Participants must not have history of gastrointestinal disease or other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications. * Participants must not have inadequate organ function, as determined by laboratory testing within the screening period. * Participants must not have active viral HBV or HCV hepatitis. Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of participants who achieve Objective Response (OR) | Up to approximately 2 years | OR is defined as confirmed complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Response Assessment in Neuro-Oncology (RANO) v2 or Modified RECIST v1.1 |
| Part 2: Number of participants with adverse events meeting protocol defined dose limiting toxicities (DLTs) criteria | Up to approximately 2 years | — |
| Part 2: Number of participants with adverse events (AE) | Up to approximately 2 years | — |
| Part 2: Number of participants with Serious AEs (SAEs) | Up to approximately 2 years | — |
| Part 2: Number of participants with treatment related AEs | Up to approximately 2 years | — |
| Part 2: Number of participants with treatment related SAEs | Up to approximately 2 years | — |
| Part 2: Number of participants with AEs leading to study treatment discontinuation | Up to approximately 2 years | — |
| Part 2: Number of participants with AEs leading to death | Up to approximately 2 years | — |
| Part 2: Number of participants with laboratory abnormalities | Up to approximately 2 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and 2: Time to objective response (TTOR) | Up to approximately 2 years | Defined as time from first dose to the date of the first documentation of objective tumor response (CR or PR) by RECIST v1.1 or RANO v2 or Modified RECIST v1.1 |
| Part 1 and 2: Duration of response (DOR) | Up to approximately 2 years | Defined as the time between the date of the first documentation of objective tumor response (CR or PR) and the date of disease progression or to death from any cause (whichever occurs first) by RECIST v1.1. or RANO v2 or Modified RECIST v1.1 |
| Part 1 and 2: Number of participants who achieve disease control (DC) | Up to approximately 2 years | Best Overall Response (BOR) of confirmed CR, confirmed PR, or stable disease (SD) for at least 4 months after start of treatment) by RECIST v1.1 or RANO v2 or Modified RECIST v1.1 |
| Part 1: Number of participants with adverse events (AE) | Up to approximately 2 years | — |
| Part 1: Number of participants with Serious AEs (SAEs) | Up to approximately 2 years | — |
| Part 1: Number of participants with treatment related AEs | Up to approximately 2 years | — |
| Part 1: Number of participants with treatment related SAEs | Up to approximately 2 years | — |
| Part 1: Number of participants with AEs leading to study treatment discontinuation | Up to approximately 2 years | — |
| Part 1: Number of participants with AEs leading to death | Up to approximately 2 years | — |
| Part 1: Number of participants with laboratory abnormalities | Up to approximately 2 years | — |
| Part 2: Number of participants who achieve Objective Response (OR) | Up to approximately 2 years | — |
| Part 1 and 2: Number of participants who achieved clinical benefit (CB) | Up to approximately 2 years | CB defined as BOR of confirmed CR, confirmed PR, or SD for at least 4 months after start of treatment by RECIST v1.1 or RANO v2 |
Countries
Belgium, Canada, China, France, Germany, Hong Kong, Ireland, Italy, Japan, Norway, South Korea, Spain, United States
Contacts
CONTACTBMS Clinical Trials Contact Center www.BMSClinicalTrials.com
CONTACTFirst line of the email MUST contain NCT # and Site #.
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Outcome results
None listed