BMS-986012 ± Nivolumab Appears Well-Tolerated in Relapsed/Refractory SCLC


Findings from the phase 1/2 CA001-030 study indicate that BMS-986012 in combination with nivolumab is well tolerated among patients with small cell lung cancer.

BMS-986012, a non-fucosylated, fully human immunoglobulin G1 monoclonal antibody, with or without nivolumab (Opdivo) yielded a manageable safety profile among patients with relapsed or refractory small cell lung cancer (SCLC), according to findings from the phase 1/2 CA001-030 study (NCT02247349).

Among patients receiving BMS-986012 monotherapy, most treatment-related adverse effects (TRAEs) were grade 1 or 2, and common grade 3 TRAEs included pruritus (5.2%), fatigue (1.3%), hypokalemia (1.3%), lower respiratory tract infections (1.3%), and myalgia (1.3%). Study investigators reported no grade 4 or 5 TRAEs in patients receiving BMS-98012 monotherapy.

There were 6 treatment-related serious AEs (SAEs) following single-agent treatment, including 1 patient who had grade 3 fatigue in the 70 mg cohort. One patient had grade 3 pruritus, 1 had grade 1 pyrexia, and 1 with a grade 2 infusion-related reaction in the 400 mg cohort. In the 1000 mg cohort, 1 patient had grade 3 pruritus and grade 3 lower respiratory tract infection.

In the combination arm, common, any grade TRAEs included pruritis (n = 27), fatigue (n = 8), dry skin (n = 8), and hypothyroidism (n = 5). A total of 3 grade 4 TRAEs were observed, including amylase increase, lipase increase, and hyponatremia.

The overall response rate (ORR) among patients receiving BMS-986012 monotherapy was 4% and 23% of patients achieved stable disease. Additionally, the median overall survival (OS) was 5.4 months (95% CI, 4.0-7.33), with a 12-month OS rate of 21.2% (95% CI, 12.0%-32.0%). Median progression-free survival (PFS) was 1.3 months (95% CI, 1.3-1.4), and the 24-week PFS rate was 12.2% (95% CI, 6.0%-20.7%).

Among patients receiving BMS-986012 plus nivolumab, the ORR was 38% (95% CI, 20.7%-57.7%), with 10 patients achieving a partial recovery, 1 patient having a complete recovery, and 3 having stable disease. The median OS for this group was 18.7 months (95% CI, 8.2-37.3). The 12-month and 24-month OS rates, respectively, were 64.5% (95% CI, 44.0%-79.1%) and 39.4% (95% CI, 21.7%-56.6%). The median PFS was 2.1 months (95% CI, 1.4-9.9), and the 24-week PFS rate was 39.3% (95% CI, 21.7%-56.5%).

Investigators of the phase 1/2 CA001-030 study evaluated BMS-986012 as monotherapy or in combination with nivolumab for adult patients with relapsed or refractory SCLC. Treatment was assessed across different dosing levels, which included 70 mg, 160 mg, 400 mg, and 1000 mg of intravenous BMS-986012 monotherapy, and 400 mg or 1000 mg of intravenous BMS-986012 plus 360 mg of intravenous nivolumab taken once every 3 weeks.

The primary end point of the study was safety. Secondary end points included ORR, duration of response, PFS, overall survival, and pharmacokinetics.

Adult patients who had a histologically or cytologically confirmed diagnosis of SCLC and received at least 1 prior line of therapy were eligible to enroll on the study.

A total of 77 patients received BMS-986012 monotherapy and 29 received BMS-986012 plus nivolumab. In each respective group, the median patient age was 63 years (range, 26-81) and 65 years (range, 46-79). Most patients in each respective group were male (60% vs 52%), White (91% vs 100%), current or former users of tobacco (97% vs 100%), and were previously treated with first-line systemic therapy (81% vs 86%).

One patient in the monotherapy cohort was antidrug anti-body (ADA)–positive at baseline, and all patients were ADA-negative at the time of postbaseline assessment. Moreover, all patients in the BMS and nivolumab combination therapy cohort were ADA-negative following postbaseline assessment.

There were 63 patient deaths in the BMS-986012 monotherapy cohort that were considered unrelated to treatment by the study investigators. There were 16 patient deaths among those receiving BMS-986012 with nivolumab, which the investigators determined to be unrelated to the combination therapy.


Chu Q, Leighl NB, Surmont V, et al. BMS-986012, an anti–fucosyl-GM1 monoclonal antibody as monotherapy or in combination with nivolumab in relapsed/refractory SCLC: results from a first-in-human phase 1/2 study. JTO and Clinical Research Reports. 2022;3(11):100400. doi:10.1016/j.jtocrr.2022.100400

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