A Phase 1/2 Study of BMS-986340 as Monotherapy and in Combination With Nivolumab or Docetaxel in Participants With Advanced Solid Tumors

Overview

BMS-936558-01 refers to nivolumab (also known as BMS-936558, MDX-1106, ONO-4538), a fully human IgG4 monoclonal antibody immune-checkpoint inhibitor targeting PD-1. The “-01” suffix has been used in early study identifiers (for example, the single‑ascending‑dose MDX‑1106‑01 study) rather than indicating a distinct molecule. Nivolumab has extensive human clinical data across cancers and other diseases. (ascopubs.org)

Mechanism of action

Nivolumab binds the programmed death‑1 (PD‑1) receptor on activated T cells and blocks interaction with PD‑L1/PD‑L2, thereby relieving inhibitory signaling and restoring antitumor T‑cell activity. Preclinical characterization and early clinical experience established on‑target immune activation with a generally manageable safety profile. (aacrjournals.org)

Efficacy

Non–small cell lung cancer (NSCLC), previously treated - Squamous histology (CheckMate 017, phase 3): Nivolumab improved median overall survival (OS) to 9.2 months vs 6.0 months with docetaxel (HR 0.59; P<0.001). Objective response rate (ORR) was 20% vs 9%; grade 3–4 treatment‑related adverse events (AEs) occurred in 7% vs 55%. Benefit was observed regardless of PD‑L1 expression. Two‑year updates showed OS rates of 23% with nivolumab vs 8% with docetaxel. (nejm.org)

• Nonsquamous histology (CheckMate 057, phase 3): Median OS 12.2 vs 9.4 months for nivolumab vs docetaxel (HR 0.73; P=0.002). Two‑year OS rates were 29% vs 16% in favor of nivolumab. (nejm.org)

Phase 1/early studies (signal-finding and subgroup analyses) - In heavily pretreated advanced NSCLC, nivolumab produced an ORR ~17% with median response duration ~17 months; 1‑ and 2‑year OS rates up to 56% and 45% at the 3 mg/kg dose cohort in exploratory analyses. (ascopubs.org)

Other indications (selected) - Ovarian cancer (platinum‑resistant, early phase): initial ASCO abstract reported activity and safety in small cohorts (1–3 mg/kg), establishing feasibility for further study. (ascopubs.org)

• Chronic hepatitis C (proof‑of‑concept): single‑dose, randomized, placebo‑controlled study showed antiviral activity in a subset, including >4‑log10 viral load reductions at 10 mg/kg and rare cases of sustained RNA negativity; this was exploratory for infectious disease rather than an approved use. (pmc.ncbi.nlm.nih.gov)

Safety

Across tumor types and lines of therapy, nivolumab’s safety profile is characterized by immune‑mediated AEs. In randomized phase 3 NSCLC trials versus docetaxel, nivolumab had markedly fewer grade 3–4 treatment‑related AEs (e.g., 7% vs 55% in CheckMate 017). Reported immune‑related AEs include pneumonitis, thyroid disorders, hepatitis, rash, and others; most were manageable with established algorithms. Long‑term pooled analyses (2‑year follow‑up) confirmed fewer high‑grade AEs with nivolumab than with docetaxel (10% vs 55%). (nejm.org)

Key pharmacokinetics

In early single‑ and multiple‑ascending‑dose studies, nivolumab displayed linear pharmacokinetics over 0.1–10 mg/kg with a terminal half‑life approximately 17–25 days and dose‑proportional exposure; body‑weight‑normalized dosing provided consistent trough concentrations. (ascopubs.org)

Notes on naming

Published abstracts and reports often use “BMS‑936558,” “MDX‑1106,” or “ONO‑4538” interchangeably for nivolumab. The “‑01” suffix appears in early study identifiers (e.g., MDX‑1106‑01) rather than denoting a separate investigational product. (ascopubs.org)

Further reading

• Nivolumab vs docetaxel in previously treated squamous NSCLC (CheckMate 017), NEJM primary report. (nejm.org)
• Nivolumab vs docetaxel in previously treated nonsquamous NSCLC (CheckMate 057), NEJM primary report and full text. (nejm.org)
• Two‑year outcomes pooled across CheckMate 017 and 057 (JCO). (pubmed.ncbi.nlm.nih.gov)
• In vitro characterization and non‑human primate toxicology of nivolumab (Cancer Immunology Research). (aacrjournals.org)
• Pharmacokinetics from early SAD/MAD studies and HCV proof‑of‑concept study (ASCO abstract; PLoS One/PMC). (ascopubs.org)
• Early NSCLC activity and subgroup analyses from phase 1 (ASCO abstracts). (ascopubs.org)

Disclaimer: This summary reflects data available in the cited sources as of October 7, 2025 and focuses on peer‑reviewed publications and conference abstracts.

Last updated: Oct 2025

Overview

Imzokitug (BMS-986340) is Bristol Myers Squibb’s investigational, afucosylated human IgG1 monoclonal antibody directed against CCR8, being developed for advanced solid tumors. A global first‑in‑human Phase 1/2 study (CA052‑002; NCT04895709) is evaluating imzokitug as monotherapy and in combination with nivolumab or docetaxel. As of October 7, 2025, the study remains active/recruiting and no peer‑reviewed human efficacy or safety outcomes for imzokitug have been publicly reported. (bmsclinicaltrials.com)

Mechanism of action

• Target: CCR8, a chemokine receptor enriched on intratumoral regulatory T cells (Tregs). In tumor samples, CCR8 expression correlates strongly with FOXP3 and is largely restricted to FOXP3hi Tregs rather than conventional effector T cells. (aacrjournals.org)
• Modality: Afucosylated anti‑CCR8 IgG1 designed to enhance antibody‑dependent cellular cytotoxicity (ADCC) and deplete CCR8+ Tregs within the tumor microenvironment, thereby relieving immunosuppression and enabling effector T‑cell activity. It also blocks CCR8–CCL1 interaction. (drugs.ncats.io)
• Preclinical data: Anti‑CCR8–mediated Treg depletion led to pro‑inflammatory remodeling of the tumor microenvironment and robust tumor growth inhibition in murine models; BMS‑986340 depleted CCR8+ Tregs in human tumor explants. (aacrjournals.org)

Clinical development

• Trial: CA052‑002 (NCT04895709), Phase 1/2, multi‑part, open‑label study assessing safety, dosing, and preliminary activity of imzokitug alone and with nivolumab or docetaxel across selected solid tumors. Recruitment began in 2021 and remains ongoing across multiple sites. (bmsclinicaltrials.com)

Efficacy

• No human efficacy results for imzokitug have been publicly disclosed in peer‑reviewed journals or major conference abstracts as of October 7, 2025. (bmsclinicaltrials.com)

Safety

• No human safety results for imzokitug have been publicly disclosed in peer‑reviewed journals or major conference abstracts as of October 7, 2025. (bmsclinicaltrials.com)

Further reading

• Preclinical rationale and tumor explant data (AACR abstract). (aacrjournals.org)
• Official BMS trial page for CA052‑002 (NCT04895709). (bmsclinicaltrials.com)
• EU Clinical Trials Register entry (EudraCT 2021‑001188‑26). (ichgcp.net)
• NCATS Drug Record for imzokitug (mechanism details, INN). (drugs.ncats.io)

Note: Other CCR8 antibodies from different sponsors have begun reporting early clinical findings, but those data are not specific to imzokitug and are therefore not summarized here. (ascopubs.org)

Last updated: Oct 2025

Inclusion Criteria:

* Fresh pre-treatment and on-treatment tumor biopsy must be provided for biomarker analysis

* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and at least 1 lesion accessible for biopsy. Fine needle biopsy, cytology, and bone lesion biopsies are not acceptable.

* Eastern Cooperative Oncology Group Performance Status of 0 or 1

* Radiographically documented progressive disease on or after the most recent therapy

* Received standard-of-care therapies, (except for Part 1C, where participants with prior docetaxel use for the advanced/metastatic setting will be excluded), including an available programmed death (ligand)-1 inhibitor known to be effective in the tumor type for which they are being evaluated

* Advanced or metastatic disease and have received, be refractory to, not be a candidate for, or be intolerant of existing therapies known to provide clinical benefit for the condition of the participant

Exclusion Criteria:

* Women who are pregnant or breastfeeding

* Primary central nervous system (CNS) malignancy

* Untreated CNS metastases

* Leptomeningeal metastases

* Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years prior to the first dose of study treatment

* Active, known, or suspected autoimmune disease

* Condition requiring systemic treatment with either corticosteroids within 14 days or other immunosuppressive medications within 30 days of the first dose of study treatment

* Prior organ or tissue allograft

* Uncontrolled or significant cardiovascular disease

* Major surgery within 4 weeks of study drug administration

* History of or with active interstitial lung disease or pulmonary fibrosis

Other protocol-defined inclusion/exclusion criteria apply