advanced solid tumour, advanced stage cutaneous melanoma and Lung/NSCLC (adenocarcinoma and squamous cell carcinoma). Other tumor histologies may also be included by the Sponsor. Solid Tumors
Conditions
Interventions
All dosing will occur every three or four weeks as follows:
- Part 1B (BMS-986218 + Nivolumab), will be administered every 4 weeks on Day 1
of each 28 days cycle.
- Part 2A (BMS-986218 monotherapy fo
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1) Participants must be at least 18 years old and have histologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent and/or unresectable) with measurable disease per RECIST v1.1 or per PCWG 3 criteria for prostate and have at least one soft-tissue lesion accessible for biopsy. b) Eastern Cooperative Oncology Group Performance Status of 0 or 1 c) The Safety Evaluation of Combination Doses of BMS-986218 with Nivolumab (Part 1B): i) Select solid tumor histologies will be permitted during dose escalation, except for participants with CNS metastases as the only site of active disease. The included histologies will be NSCLC (squamous or adenocarcinoma), gastric adenocarcinoma (including GE junction), TNBC, CRC (adenocarcinoma), pancreatic adenocarcinoma, metastatic castrate resistant prostate adenocarcinoma, urothelial carcinoma or SCCHN (oral cavity, pharyngeal, oropharyngeal, hypopharynx, or laryngeal tumors only). Any other cancers of the head and neck, including salivary gland and neuroendocrine tumors, are excluded from enrollment. Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx, SCC or other cancers of the skin of head and neck, and non-squamous histologies are not allowed. Additional tumor histologies may also be included by the Sponsor. ii) Participants must have received, and then progressed, relapsed, or been intolerant to at least 2 systemic therapy regimens with proven survival benefit in the advanced or metastatic setting according to tumor type, where available. If the participant refuses or is not eligible for these regimens, the reason must be documented in the medical record. However, if anti-PD-1 therapy is approved in a given indication, participants are eligible to receive this treatment as part of the combination regimen in this study prior to having completed 2 prior systemic therapy regimens after discussion and agreement with the Medical Monitor (or designee). For hormone-sensitive cancers, all previously received and available hormonal therapies will be considered as 1 systemic therapy regimen for the purposes of eligibility. For prostate cancer, only metastatic castrate resistant prostate cancer is allowed. d) The Randomized BMS-986218 Monotherapy Cohort Expansion in Cutaneous Melanoma (Part 2A): i) Participants with advanced stage cutaneous melanoma who have received standard therapies with proven survival benefit including prior immunotherapy with an anti-PD-1 or anti-PD-L1 containing regimen and must have progressive or recurrent disease after prior PD-1/PD-L1 directed therapy. Participants must not have received prior anti-CTLA-4 therapy in the advanced or metastatic setting. Additionally, participants with cutaneous melanoma must have also been offered mutation-directed therapy, if indicated, that has proven survival benefit; if a participant refuses such therapy, it must be documented in the medical record. No more than 1 intervening therapy is allowed but not required between prior anti-PD-1/anti-PD-L1 containing regimen and BMS-986218. No more than 70% of the randomized participants should have had progression of disease within a period of 6 months of start of therapy with anti-PD-1/PD-L1 agent. Only cutaneous melanoma is allowed. Mucosal an
Exclusion criteria
Exclusion criteria: Participants with primary CNS malignancies, or tumors with CNS metastases as the only site of disease, will be excluded. Participants with controlled brain metastases; however, will be allowed to enroll. Controlled brain metastases are defined as no radiographic progression for at least 4 weeks following radiation and/or surgical treatment (or 4 weeks of observation if no intervention is clinically indicated), and no longer taking steroids for at least 2 weeks prior to first dose of study treatment, and with no new or progressive neurological signs and symptoms.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Outcome Measures: Safety assessments will be based on comprehensive medical review of adverse event reports, vital sign measurements, ECGs, physical examinations, oxygen saturation, and results of laboratory tests. Adverse events will be assessed continuously during the study and for 100 days after the last treatment. The incidence of observed adverse events will be tabulated and reviewed for potential significance and clinical importance. Efficacy Measures: Disease assessment with CT and/or MRI, as appropriate, will be performed at baseline and Part 2A : Tumour imaging assessment to be performed at 12 weeks from the first dose, regardless of dose delays, if any (+/- 1 week), prior to initiating the next cycle of treatment. Part 2B, 2C and 2D : Tumour imaging assessment to be performed Q8W from the first dose (+/- 1 week), prior to initiating next cycle of treatment. After that, subsequent tumour imaging assessments to be performed Q8W (+/- 1 week), prior to initiating the next cycle of treatment. Participants who remain free of subsequent therapy will undergo tumour imaging assessment Q8W (+/- 1 week) until subsequent tumour-directed therapy is initiated or until 48 weeks after discontinuation of trial treatment/EOT visit, and then Q12W (+/- 2 weeks) for a total duration of 2 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic Measures: Serial serum samples will be collected from all subjects at specified time points to evaluate concentrations of BMS-986218. PK parameters such as Cmax, Ctrough, Tmax, T-HALF, AUC (TAU), CLT, and accumulation index (AI) will be derived, if feasible, from serum concentration versus time data. Parameters that May be Assessed Following the Dose Administration in Cycle 3: CLT, Css-avg-AI and T-HALF. Imaging Measures: The same imaging modality is to be used for all assessments, per RECIST v1.1 (Appendix 5) or per PCWG 3 criteria for prostate (Appendix 12). Tumor assessment to be performed prior to initiating next cycle of treatment. CT and MRI scans should be acquired with slice thickness of 5 mm or less with no intervening gap (contiguous). Every attempt should be made to image each participant using an identical acquisition protocol on the same scanner. Immunogenicity Measures: Serum samples for BMS-986218, ipilimumab, and nivolumab ADA and cytokines will be collected from all participants at specified timepoints. Biomarker Measures: Biomarker measures of baseline and on-treatment peripheral blood, serum, and tumor samples will be used to identify PD markers associated with treatment. Additional biomarkers related to mechanism of action, safety biomarkers, and associations with response to BMS-986218, alone and in combination with nivolumab, will be explored. Peripheral blood and tumor tissue will be collected prior to therapy and on-treatment. Biopsies must be performed at the time of progression or suspected progression for participants on study treatment for more than 4 cycles, and tumor samples (block or slides) must be submitted for analysis. If biomarker samples are drawn but study treatment(s) is not administered, samples will be retained. A detailed description of each assay system is described below and a schedule of pharmacodynamic evaluations is provided in the protocol. | — |
Countries
Netherlands
Outcome results
None listed