BMS-986156 / BMS - LARVOL DELTA

Rationale and feasibility of a rapid integral biomarker program that informs immune-oncology clinical trials: the ADVISE trial. (PubMed, J Immunother Cancer) - P1 | "Actualization of a patient-specific I-O combination treatment selection strategy is feasible, however, determination of de novo integral biomarker thresholds of novel I-O targets to facilitate effective treatment of PD-1-refractory cancer remains fraught. These data emphasize the difficulty of integral biomarker development for I-O in translating from immunotherapy treatment-naïve biospecimens to the selection of patients in the PD-1-refractory state."

Biomarker • IO biomarker • Journal • Gastric Cancer • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • CD8 • CSF1R • FOXP3 • IDO1 • LAG3 • PD-L1 • TNFA

BMS-986156, Ipilimumab, and Nivolumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Lung/Chest or Liver Cancers (clinicaltrials.gov) - P1/2 | N=51 | Completed | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Completed | Trial completion date: Aug 2027 ➔ Apr 2025 | Trial primary completion date: Aug 2027 ➔ Apr 2025

Trial completion • Trial completion date • Trial primary completion date • Tumor mutational burden • Hepatology • Liver Cancer • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Phase I/II study of BMS-986156 with ipilimumab or nivolumab with or without stereotactic ablative radiotherapy in patients with advanced solid malignancies. (PubMed, J Immunother Cancer) - P1/2 | "BMS-986156 was well-tolerated with ipilimumab, nivolumab, with or without SABR. Outcomes were encouraging in this population, as more than half of patients had stable disease/partial response."

Journal • Metastases • P1/2 data • Oncology • Solid Tumor • CTLA4 • TNFA

Final Report of a Phase I/II Study of BMS-986156 (Glucocorticoid-Induced TNFR-Related Gene [GITR] Agonist) with Ipilimumab or Nivolumab with/without Stereotactic Ablative Radiotherapy in Patients with (ASTRO 2024) - P1/2 | "BMS-986156 was well-tolerated with Ipilimumab, Nivolumab, with or without SABR. Overall, more than half of patients had stable disease/partial response. The disease control rate and abscopal effect observed in those receiving SABR seem higher than reported in prior studies."

Clinical • P1/2 data • Oncology • Solid Tumor

BMS-986156, Ipilimumab, and Nivolumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Lung/Chest or Liver Cancers (clinicaltrials.gov) - P1/2 | N=68 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Aug 2024 ➔ Aug 2027 | Trial primary completion date: Aug 2024 ➔ Aug 2027

Metastases • Trial completion date • Trial primary completion date • Tumor mutational burden • Gastrointestinal Cancer • Hepatology • Liver Cancer • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

BMS-986156, Ipilimumab, and Nivolumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Lung/Chest or Liver Cancers (clinicaltrials.gov) - P1/2 | N=68 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Aug 2023 ➔ Aug 2024 | Trial primary completion date: Aug 2023 ➔ Aug 2024

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Liver Cancer • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • TMB

Pharmacodynamic activity of BMS-986156, a glucocorticoid-induced TNF receptor-related protein agonist, alone or in combination with nivolumab in patients with advanced solid tumors. (PubMed, ESMO Open) - P1/2 | "Despite the robust evidence of peripheral PD activity of BMS-986156, with or without nivolumab, limited evidence of T- or NK cell activation in the tumor microenvironment was observed. The data therefore explain, at least in part, the lack of clinical activity of BMS-986156 with or without nivolumab in unselected populations of cancer patients."

Combination therapy • IO biomarker • Journal • Metastases • PK/PD data • Immune Modulation • Oncology • Solid Tumor • CD8 • PD-L1 • TNFA

BMS-986156, Ipilimumab, and Nivolumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Lung/Chest or Liver Cancers (clinicaltrials.gov) - P1/2 | N=68 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Tumor mutational burden • Gastrointestinal Cancer • Hepatology • Liver Cancer • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • TMB

Preliminary results of a phase I/IIa study of BMS-986156 (glucocorticoid-induced tumor necrosis factor receptor–related gene [GITR] agonist), alone and in combination with nivolumab in pts with advanced solid tumors. (ASCO 2017) - P1/2; "This is the first report of clinical data with an anti-GITR mAb ± a PD-1 inhibitor.BMS-986156 ± nivolumab was well tolerated, with no DLTs and low immunogenicity. Antitumor activity was observed with BMS-986156 + nivolumab at doses predicted to be biologically active. Further evaluation of this combination in pts with advanced solid tumors is ongoing."

Combination therapy • P1/2 data • Biosimilar • Immunology • Oncology

Phase 1, open-label, adaptive biomarker trial that informs the evolution of combination immuno-oncology (IO) therapies (ADVISE), a precision IO approach to personalized medicine. (ASCO 2018) - P1; "Patients will receive nivolumab in combination with a second IO agent that is implicated in tumor immune escape (lirilumab [anti-KIR], relatlimab [anti?LAG-3], cabiralizumab [anti?CSF-1R], ipilimumab [anti?CTLA-4], BMS-986205 [IDO-1 inhibitor], or BMS-986156 [anti-GITR]) or nivolumab with stereotactic body radiation therapy (for noninflamed tumors). The primary endpoint is the ratio of patients with qualified tumor biopsy specimens at baseline providing sufficient biomarker data and analysis time to guide treatment decisions. Other endpoints include safety, preliminary clinical activity, and biomarker analyses."

Biomarker • Clinical • IO biomarker • P1 data • PD(L)-1 Biomarker • Solid Tumor

An Investigational Immuno-therapy Study of Experimental Medication BMS-986156, Given by Itself or in Combination With Nivolumab in Patients With Solid Cancers or Cancers That Have Spread. (clinicaltrials.gov) - P1/2; N=331; Completed; Sponsor: Bristol-Myers Squibb; Active, not recruiting ➔ Completed; Trial completion date: Jan 2020 ➔ Dec 2020; Trial primary completion date: Jan 2020 ➔ Dec 2020

Clinical • Combination therapy • Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

ADVISE: An Adaptive Study to Match Patients With Solid Tumors to Various Immunotherapy Combinations Based Upon a Broad Biomarker Assessment (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Bristol-Myers Squibb; Not yet recruiting ➔ Recruiting; Trial primary completion date: Mar 2021 ➔ Jan 2020

Enrollment open • Trial primary completion date • Biosimilar • Immunology • Oncology • Solid Tumor

Safety, Tolerability, and Potential Clinical Activity of a Glucocorticoid-Induced TNF Receptor-Related Protein Agonist Alone or in Combination With Nivolumab for Patients With Advanced Solid Tumors: A Phase 1/2a Dose-Escalation and Cohort-Expansion Clinical Trial. (PubMed, JAMA Oncol) - P1/2; "Based on this cohort, BMS-986156 appears to have had a manageable safety profile, and BMS-986156 plus nivolumab demonstrated safety and efficacy comparable to historical data reported for nivolumab monotherapy. ClinicalTrials.gov identifier: NCT02598960."

Biomarker • Clinical • Combination therapy • Journal • P1/2 data • PD(L)-1 Biomarker • FOXP3

BMS-986156, Ipilimumab, and Nivolumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Lung/Chest or Liver Cancers (clinicaltrials.gov) - P1/2; N=60; Recruiting; Sponsor: M.D. Anderson Cancer Center; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • PD(L)-1 Biomarker • Tumor Mutational Burden

An Investigational Immuno-therapy Study of Experimental Medication BMS-986156, Given by Itself or in Combination With Nivolumab in Patients With Solid Cancers or Cancers That Have Spread. (clinicaltrials.gov) - P1/2; N=310; Active, not recruiting; Sponsor: Bristol-Myers Squibb; Trial completion date: May 2020 ➔ Jan 2020

Clinical • Combination therapy • Trial completion date

BMS-986156, Ipilimumab, and Nivolumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Lung/Chest or Liver Cancers (clinicaltrials.gov) - P1/2; N=60; Not yet recruiting; Sponsor: M.D. Anderson Cancer Center

Clinical • New P1/2 trial • PD(L)-1 Biomarker • Tumor Mutational Burden