Patients with Advanced Solid Tumors (see protocol for tumor types) advanced solid tumors cancer
Conditions
Interventions
The medicinal interventions include Nivolumab/Anti-Lag-3 combination therapy.
BMS will supply everything to the site taking part.
The Treatment Period consists of up to twelve 8-week treatment cycl
Sponsors
Bristol-Myers Squibb
Eligibility
Age
12 Years to 99 Years
Inclusion criteria
Inclusion criteria: -For Dose escalation: subjects with cervical, ovarian, bladder and CRC, head and neck, gastric and hepatocellular cancer naive to immuno-oncology agents; 1st line melanoma and NSCLC; NSCLC progressing while on or after therapy with anti-PD1/anti-PDL-1 and melanoma subjects progressed while-on or after treatment with anti-PD1 or anti-PDL1 with/out anti-CTLA-4. -For Dose Expansion: all of the above in escalation except for cervical, ovarian bladder and CRC -Progressed, or been intolerant to, at least one standard treatment regimen -Received any number of prior treatment regimens -ECOG performance status of 0 or 1 -At least 1 lesion with measurable disease at baseline -Availability of an existing tumor biopsy sample (or consent to allow pre-treatment tumor biopsy if sample not available
Exclusion criteria
Exclusion criteria: - Primary CNS tumors or solid tumors with CNS metastases as the only site of active disease, - Autoimmune disease, - Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent, - Uncontrolled CNS metastases
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: The primary endpoint of this Phase 1/2a study is safety as measured by the rate of AEs, serious adverse events (SAEs), deaths, and laboratory abnormalities, assessed during treatment and for up to for 135 days after the last treatment. All subjects who receive at least one dose of BMS-986016 or nivolumab will be analyzed for safety. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints: Efficacy: The best overall response (BOR), objective response rate (ORR, i.e., CR + PR), disease control rate (DCR) at 12 weeks, duration of response (DOR), and progression-free survival (PFS) will be assessed based on RECIST v1.1 criteria. Landmark PFS rates at pre-specified time points, e.g., 24 weeks, will be assessed. Pharmacokinetics: Select BMS-986016 PK parameters, such as Cmax, Ctrough, Tmax, AUC (TAU), CLT, and AI, will be assessed from concentration-time data during Cycle 1 and Cycle 3. Immunogenicity: The proportion of subjects who develop specific ADA to either BMS-986016 or Nivolumab will be measured during treatment and for up to 135 days after their last treatment in post-treatment follow-up. ECG: In Parts A and B, QTc will be assessed by a central reader for ECG collected at follow-up visit 1, as well as on Day 1 of Cycle 1 and Cycle 3 at the pre-dose and 4-hour post-dose time points. Exploratory Endpoints: Biomarkers: Biomarker endpoints from peripheral blood may include, but not limited to, measures such as levels of soluble factors, as well characterization by immunophenotyping, at each scheduled timepoint. Biomarker endpoints from tumor biopsies may include but will not be limited to measures such as level of immune cell infiltration, somatic mutational load, expression of IFN response genes, functional status and diversity of T cell receptor repertoire, and expression of lymphocyte activation gene 3 (LAG-3), major histocompatibility complex (MHC) class II, PD-1, and PD-L1. Pharmacokinetics: PK parameters will include nivolumab concentration-time data at select trough (Ctrough) and end-of-infusion (EOI) timepoints based on measurements collected for up to 135 days during the post-treatment follow-up. Efficacy: Landmark overall survival will be an exploratory efficacy endpoint in subjects treated with BMS-986016 alone and in combination with nivolumab. | — |
Countries
Netherlands
Outcome results
None listed