Abstract 3419
Background
Fucosyl-GM1 (Fuc-GM1), a ganglioside with abundant yet restricted expression on the cell surface of SCLCs, is a potential target for therapeutic approaches. Here we present preliminary results from a Phase 1/2 study of BMS-986012, a first-in-class fully human IgG1 monoclonal antibody with enhanced ADCC that specifically binds to Fuc-GM1, for the treatment of SCLC.
Methods
Patients (pts) with relapsed/refractory SCLC after at least one line of prior therapy were enrolled. BMS-986012 was administered IV at flat doses of 70, 160, 400, and 1000 mg every 3 weeks (wk) during dose escalation. Pharmacokinetics (PK) and anti-drug antibodies (ADA) were assessed during cycle 1.
Results
Twenty-nine pts were treated across all doses. Median age was 63 yr (range: 26–81); 55% were female; 95% had a smoking history. Pts had received up to five lines of prior therapy; 52% had one prior line; 48% had 2 or more two prior lines. Nine pts were platinum refractory (≤3 mo from end of first line therapy to progression). No dose limiting toxicities or treatment-related grade 4 or 5 adverse events occurred. Treatment-related adverse events occurring in >10% of pts were pruritus, decreased appetite, and rash. Preliminary PK analysis suggests a linear dose-exposure relationship (Table). No ADAs were detected.
Summary of Single Dose Exposures of BMS-986012
| 70 mg | 160 mg | 400 mg | 1000 mg | |
|---|---|---|---|---|
| AUC (0–504 hr), ug*hr/mL Geom. Mean (CV), % | 4434 (31) | 8544 (23) | 19642 (47) | 44677 (23) |
| Cmax, ug/mL Geom. Mean (CV), % | 28 (28) | 74 (125) | 145 (26) | 348 (23) |
Geom. = Geometric; CV = coefficient of variation
One confirmed complete response (CR; duration 53 wk; 70 mg dose level) and one confirmed partial response (PR; duration 17 wk; 400 mg dose level) were observed. Stable disease (SD) was reported in 4 pts. The CR and 2 SD occurred among the 9 platinum refractory pts.Conclusions
BMS-986012 demonstrates a manageable safety profile and resulted in objective responses in relapsed SCLC, including platinum refractory pts. Preliminary PK analysis showed dose-proportional and linear increase in exposure with moderate to high variability. Dose expansion is currently enrolling at 400 and 1000 mg.
Clinical trial identification
NCT02247349
Legal entity responsible for the study
Sponsored by Bristol-Myers Squibb
Funding
Sponsored by Bristol-Myers Squibb
Disclosure
Q.S-C. Chu: Personal fees from BMS and Lilly (advisory boards), Novartis (advisory board and consultancy), and Astra Zeneca, Merck (advisory and consultancy). Grants and personal fees from BI (Research Grant and advisory board). L. Krug: Grants from Bristol-Myers Squibb, during the conduct of the study; other from Bristol-Myers Squibb, outside the submitted work. C. Rudin: Personal fees from Bristol Myers Squibb, Celgene, Novartis, Medivation, and Merck, outside the submitted work. D. Lathers: Employee & Shareholder at BMS. P. Basciano: Personal fees from Bristol-Meyers Squibb, outside the submitted work as a Study Sponsor. P.M. Fracasso: Employee of BMS. P. Phillips: Employee of Bristol-Myers Squibb. N. Ready: Personal fees from Bristol Myers Squibb, Celgene, Novartis, Medivation, and Merck, outside the submitted work. All other authors have declared no conflicts of interest.