MC# 22-10 - A Phase I First-in-human Study of BMS-986406 as Monotherapy and Combination Therapies in Participants with Advanced Malignant Tumors
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Agent(s): BMS-986406, Nivolumab
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Disease Type(s): Bladder, Gastric, Melanoma, Mesothelioma, Ovarian, Pancreatic, Prostate, Sarcoma, Renal, Lung-NSCLC, Breast- Triple Negative, Squamous Cell Carcinoma of Head and Neck, Gastroesophageal Junction
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Phase(s): I
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Drug Classification(s): Immunotherapy, Monoclonal Antibody, Targeted Therapy
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Molecular Target(s): LILRB2
Mechanism of Action
BMS-986406 is an anti-LILRB2 antibody that reprograms the immune-suppressive macrophages which enhances anti-tumor immunity in the tumor microenvironment.
Nivolumab is an IgG4 kappa human monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Purpose
In this study, the sponsor and investigators want to learn:
- How much of BMS-986406 can be given with an acceptable level of side effects and in combination with nivolumab
- The effects of BMS-986406 (good and bad) and in combination with nivolumab
- How much of BMS-986406 is absorbed into the blood and how fast it is removed
- If the body’s immune system has a response to BMS-986406 and in combination with nivolumab
Inclusion Criteria
- Participants with histologically or cytologically confirmed locally advanced unresectable, metastatic, or recurrent malignant tumor. Eligible tumor types are as follows: NSCLC, RCC, PDAC, gastric/gastroesophageal junction, CRPC, ovarian, SCCHN, bladder, melanoma, mesothelioma, TNBC, and soft tissue sarcoma, except for participants with tumors with CNS metastases as the only site of active disease.
- Participants must have measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), PCWG3 (for prostate cancer), or mRECIST (for mesothelioma):
- Mesothelioma tumor thickness perpendicular to the chest wall or mediastinum that can be measured in up to 2 positions at 3 separate levels on transverse cuts of CT scan (cuts must be at least 10 mm apart), for a total of up to 6 measurements. Each single tumor measurement must be at least 10 mm to qualify as measurable disease and contribute to the sum that defines the pleural measurement.
- Non-pleural metastatic target lesions measured uni-dimensionally as per RECIST v1.1 criteria
- Participants who present without pleural lesions that can be considered measurable, but with metastatic lesions meeting criteria for target lesion by RECIST v1.1 criteria may be considered for inclusion after consultation with the Medical Monitor
- Participants must have received, become refractory to, ineligible for, or intolerant of existing therapy(ies) considered as standard of care for the condition of the participant
- All participants must be anti-ILT4 naive. Prior anti-PD-1 or anti-PD-L1 exposure is allowed.
- Disease amenable to mandatory baseline biopsy collection at screening. Participants must have a lesion that can be biopsied at an acceptable clinical risk as judged by the Investigator to be eligible for the study. Fine needle aspirates and other cytology specimens are not allowed. An unsuccessful fresh tumor biopsy at screening will not exclude participants from receiving or continuing study treatment. The biopsy sample should be submitted to central laboratory prior to treatment assignment except if biopsy was attempted but was not completed due to safety concerns.
- Participants must have experienced radiographically documented disease progression on or after the most recent therapy
- Participants must have an Eastern Cooperative Oncology Group Performance Status of 0 or 1
Exclusion Criteria
- Systemic anti-cancer agents (cytotoxic and non-cytotoxic), unless at least 4 weeks or 5 half-lives (whichever is shorter) have elapsed from the last dose of prior anti-cancer therapy and prior to the initiation of study intervention. If 5 half-lives is shorter than 4 weeks, agreement with the Sponsor/Medical Monitor (or designee) is mandatory.
- Prior immune therapy treatments, unless at least 4 weeks or 5 half-lives (whichever is shorter) have elapsed from the last dose of immune therapy and initiation of study intervention
- Has participated in a study of an investigational agent and has received study intervention or has used an investigational device within 28 days or 5 half-lives (whichever is shorter) of initiation of study intervention
- Any major surgery within 4 weeks of study intervention administration. Note: Participants must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study intervention.
- Prior participation in an anti-ILT4 clinical trial
- Treatment with complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks prior to first study treatment. Such medications are permitted if they are used as supportive care.
- Prior radiation therapy within 2 weeks prior to first study treatment. Participants must have recovered (ie, Grade ≤1 or at baseline) from radiation-related toxicities prior to first study treatment.
- Treatment with any live / attenuated vaccine within 30 days of first study treatment. The administration of a live COVID-19 vaccine is prohibited up to 7 days prior to the initiationof study treatment.
- Previous COVID-19 vaccine (including booster) within 7 days of Cycle 1 Day 1. For vaccines requiring more than 1 dose, the full initial series (eg, both doses of a 2-dose series) should be completed prior to C1D1 when feasible and when a delay in Cycle 1 Day 1 would not put the study participant at risk.
Location
- Dallas, TX - Mary Crowley Cancer Research - Medical City
