linrodostat (BMS-986205) / BMS, Ono Pharmaceutical - LARVOL DELTA

Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck (clinicaltrials.gov) - P2 | N=65 | Terminated | Sponsor: Thomas Jefferson University | N=45 ➔ 65 | Active, not recruiting ➔ Terminated; Study was terminated early due to toxicity concerns by the Sponsor.

Enrollment change • IO biomarker • Trial termination • Head and Neck Cancer • Laryngeal Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

CA017-056: Study of BMS-986205 and Nivolumab in Endometrial Cancer or Endometrial Carcinosarcoma That Has Not Responded to Treatment (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2021 ➔ Sep 2022 | Trial primary completion date: Sep 2021 ➔ Sep 2022

Trial completion date • Trial primary completion date • Carcinosarcoma • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Carcinosarcoma • Oncology • Sarcoma • Solid Tumor

Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck (clinicaltrials.gov) - P2 | N=45 | Active, not recruiting | Sponsor: Thomas Jefferson University | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Head and Neck Cancer • Laryngeal Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

CA017-056: Study of BMS-986205 and Nivolumab in Endometrial Cancer or Endometrial Carcinosarcoma That Has Not Responded to Treatment (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P2 trial • Carcinosarcoma • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Carcinosarcoma • Gynecologic Cancers • Oncology • Sarcoma • Solid Tumor

Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck (clinicaltrials.gov) - P2 | N=45 | Terminated | Sponsor: Thomas Jefferson University | Trial completion date: Dec 2025 ➔ Jun 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2025 ➔ Jun 2024; Study was terminated early due to toxicity concerns by the Sponsor.

IO biomarker • Trial completion date • Trial primary completion date • Trial termination • Head and Neck Cancer • Laryngeal Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

CA017-056: Study of BMS-986205 and Nivolumab in Endometrial Cancer or Endometrial Carcinosarcoma That Has Not Responded to Treatment (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2025 ➔ Sep 2026 | Trial primary completion date: Sep 2025 ➔ Sep 2026

Trial completion date • Trial primary completion date • Carcinosarcoma • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Carcinosarcoma • Oncology • Sarcoma • Solid Tumor

CA017-056: Study of BMS-986205 and Nivolumab in Endometrial Cancer or Endometrial Carcinosarcoma That Has Not Responded to Treatment (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2024 ➔ Sep 2025 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Carcinosarcoma • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Carcinosarcoma • Oncology • Sarcoma • Solid Tumor

CA017-056: Study of BMS-986205 and Nivolumab in Endometrial Cancer or Endometrial Carcinosarcoma That Has Not Responded to Treatment (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Recruiting ➔ Active, not recruiting | N=50 ➔ 24

Enrollment change • Enrollment closed • Carcinosarcoma • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Carcinosarcoma • Oncology • Sarcoma • Solid Tumor

Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck (clinicaltrials.gov) - P2 | N=48 | Not yet recruiting | Sponsor: Thomas Jefferson University

IO biomarker • New P2 trial • Head and Neck Cancer • Laryngeal Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck (clinicaltrials.gov) - P2 | N=45 | Active, not recruiting | Sponsor: Thomas Jefferson University | Terminated ➔ Active, not recruiting | Trial completion date: Jun 2024 ➔ Dec 2025 | Trial primary completion date: Jun 2024 ➔ Dec 2025

Enrollment closed • IO biomarker • Trial completion date • Trial primary completion date • Head and Neck Cancer • Laryngeal Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

CA017-056: Study of BMS-986205 and Nivolumab in Endometrial Cancer or Endometrial Carcinosarcoma That Has Not Responded to Treatment (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2023 ➔ Sep 2024 | Trial primary completion date: Sep 2023 ➔ Sep 2024

Trial completion date • Trial primary completion date • Carcinosarcoma • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Carcinosarcoma • Oncology • Sarcoma • Solid Tumor

Nivolumab and BMS986205 in Treating Patients With Stage II-IV Squamous Cell Cancer of the Head and Neck (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Thomas Jefferson University | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2019 ➔ Apr 2019

Enrollment open • IO biomarker • Trial initiation date • Head and Neck Cancer • Laryngeal Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

CA017-056: Study of BMS-986205 and Nivolumab in Endometrial Cancer or Endometrial Carcinosarcoma That Has Not Responded to Treatment (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2026 ➔ Sep 2027 | Trial primary completion date: Sep 2026 ➔ Sep 2027

Trial completion date • Trial primary completion date • Carcinosarcoma • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Carcinosarcoma • Oncology • Sarcoma • Solid Tumor

CA017-056: Study of BMS-986205 and Nivolumab in Endometrial Cancer or Endometrial Carcinosarcoma That Has Not Responded to Treatment (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Sep 2022 ➔ Sep 2023 | Trial primary completion date: Sep 2022 ➔ Sep 2023

Trial completion date • Trial primary completion date • Carcinosarcoma • Endometrial Adenocarcinoma • Endometrial Cancer • Endometrial Carcinosarcoma • Oncology • Sarcoma • Solid Tumor

Heterocyclic scaffolds targeting IDO1: progress in medicinal chemistry and clinical development. (PubMed, Future Med Chem) - "IDO1 inhibitors were classified into diverse scaffolds, including indoles, imidazoles, phenyl urea-benzimidazoles, azoles, imidazopyridines, benzofurans, quinolines, pyrimidines, erlotinib-based analogues, naphthoquinones, hydroxyamidine derivatives, quinazolines, and sulfonamide chromone-oxime analogues. Clinically investigated inhibitors such as indoximod, epacadostat, navoximod, LY3381916, linrodostat, and PF-06840003 were also evaluated for therapeutic outcomes. This review provides an updated overview of IDO1 inhibitor design and development, offering valuable insights into scaffold optimization and future directions for developing effective anticancer agents targeting tumor immunosuppression."

Journal • Review • Oncology • IDO1

Nivolumab combination therapies in patients with advanced gastric and gastroesophageal junction cancer: the phase II FRACTION gastric cancer study. (PubMed, ESMO Open) - "While ORR did not meet prespecified expansion criteria in any treatment arm, the safety profile of the combinations was manageable. FRACTION-GC represents a novel adaptive protocol for testing multiple combination immunotherapies."

Journal • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • IDO1 • LAG3

ENERGIZE: A Study to Compare Chemotherapy Alone Versus Chemotherapy Plus Nivolumab or Nivolumab and BMS-986205, Followed by Continued Therapy After Surgery With Nivolumab or Nivolumab and BMS-986205 in Participants With Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P3 | N=855 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed | Trial completion date: Dec 2027 ➔ Apr 2026

Trial completion • Trial completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Phase 1 evaluation of patients with newly diagnosed glioblastoma treated with radiation, nivolumab, and IDO1 enzyme inhibitor BMS-986205. (PubMed, Clin Cancer Res) - P1 | "This single arm small phase 1 trial establishes a safety profile and RP2D for RT in combination with nivolumab and BMS-986205 for newly diagnosed MGMT-unmethylated GBM patients. (ClinicalTrials.gov: NCT04047706)."

Journal • P1 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • IDO1 • MGMT

Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor of Survival Outcomes in Head and Neck Squamous Cell Carcinoma Receiving Neoadjuvant Immunotherapy. (PubMed, Cancer Med) - "Low NLR was independently associated with improved OS and DFS among patients with HNSCC who received neoadjuvant ICI. These findings suggest the potential utility of the NLR in improving patient selection."

Biomarker • IO biomarker • Journal • Retrospective data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Artemether and Euphorbia Factor L9 suppress kynurenine production through distinct effects on Tryptophan metabolism. (PubMed, Biochem J) - "Notably ouabain, a regulator of IDO1 levels, and Linrodostat, a clinically approved IDO1 inhibitor, revealed distinct metabolic profiles, with ouabain and EFL9 showing the largest overlap. Importantly, the kynurenine-suppressing activities of artemether and EFL9 were observed in non-transformed primary mammary epithelial cells and also lung cancer cells. Overall, our findings set the foundation for future studies exploring the use of artemether or EFL9 as novel Trp metabolism-targeting therapeutics."

Journal • Breast Cancer • Infectious Disease • Lung Cancer • Metabolic Disorders • Oncology • Solid Tumor • Triple Negative Breast Cancer

RELATIVITY-048: An Investigational Study of Immunotherapy Combinations in Participants With Solid Cancers That Are Advanced or Have Spread (clinicaltrials.gov) - P1/2 | N=255 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Trial primary completion date: Apr 2024 ➔ Nov 2026

Trial primary completion date • Oncology • Solid Tumor

RELATIVITY-048: An Investigational Study of Immunotherapy Combinations in Participants With Solid Cancers That Are Advanced or Have Spread (clinicaltrials.gov) - P1/2 | N=255 | Active, not recruiting | Sponsor: Bristol-Myers Squibb | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2024 ➔ Nov 2026 | Trial primary completion date: Jan 2023 ➔ Apr 2024

Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

RELATIVITY-048: An Investigational Study of Immunotherapy Combinations in Participants With Solid Cancers That Are Advanced or Have Spread (clinicaltrials.gov) - P1/2 | N=184 | Recruiting | Sponsor: Bristol-Myers Squibb | Trial completion date: Feb 2023 ➔ Jul 2024

Trial completion date • Oncology • Solid Tumor

RELATIVITY-048: An Investigational Study of Immunotherapy Combinations in Participants With Solid Cancers That Are Advanced or Have Spread (clinicaltrials.gov) - P1/2 | N=229 | Completed | Sponsor: Bristol-Myers Squibb | Active, not recruiting ➔ Completed | Trial completion date: Nov 2026 ➔ Feb 2025 | Trial primary completion date: Nov 2026 ➔ Feb 2025

Trial completion • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

RELATIVITY-048: An Investigational Study of Immunotherapy Combinations in Participants With Solid Cancers That Are Advanced or Have Spread (clinicaltrials.gov) - P1/2 | N=230 | Recruiting | Sponsor: Bristol-Myers Squibb | Not yet recruiting ➔ Recruiting

Enrollment open • Oncology • Solid Tumor