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O21 - SCLC II (ID 119)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
O21.05 - A multicenter, double-blind, placebo-controlled, randomized phase 2 study of ganitumab or rilotumumab with platinum-based chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (SCLC) (ID 725)
16:15 - 17:45 | Author(s): S. Dubey
The type 1 insulin-like growth factor receptor (IGF1R) and MET, the receptor for hepatocyte growth factor (HGF)/scatter factor, appear to play key roles in SCLC. Ganitumab and rilotumumab are investigational, fully human monoclonal antibodies targeting IGF1R and HGF, respectively. A phase 1b/2 study evaluated ganitumab or rilotumumab combined with etoposide plus carboplatin (CE) or cisplatin (PE) in extensive-stage SCLC. The phase 1b results were previously reported (Lorigan et al. Ann Oncol 2010;21[supplement 8]: abstract 444P). Here, the phase 2 results are reported.
Key eligibility criteria: ≥18 years, confirmed SCLC, ECOG performance status ≤1, no prior chemotherapy. Patients were randomized 1:1:1 to receive blinded investigational product (IP) either ganitumab (18 mg/kg IV, day 1) or rilotumumab (15 mg/kg IV, day 1) or placebo, with etoposide (100 mg/m IV, days 1-3) plus, at investigator’s discretion, either carboplatin (AUC=5 mg/mL*minute IV, day 1) or cisplatin (75 mg/m IV, day 1) every three weeks for 4-6 cycles followed by IP monotherapy. Patients were stratified by gender and chemotherapy (CE; PE). Primary endpoint: overall survival (OS). Key secondary endpoints included progression-free survival (PFS), objective response rate (ORR), adverse events (AEs), pharmacokinetics.
185 patients (ganitumab/rilotumumab/placebo: 62/62/61) were enrolled between 2 February 2010 and 12 January 2011. Male: 77%/76%/77%. Median age: 60/61/61 years. More patients received carboplatin (41/40/40) than cisplatin (21/22/21). Most common reason for discontinuation of IP was disease progression (69%/61%/74%). Among 179 patients (59/61/59) who received IP, the most frequent any grade AEs (occurring in ≥30% of patients in any arm) were neutropenia (69%/59%/71%), anemia (39%/34%/36%), nausea (41%/30%/22%), alopecia (41%/23%/27%), thrombocytopenia (22%/30%/12%), and vomiting (19%/10%/31%). Grade ≥3 AEs and serious AEs were reported in 69%/72%/80% and 39%/38%/36% of patients, respectively. There were three IP-related grade 5 AEs: cardiac arrest (rilotumumab, n=1), febrile neutropenia (rilotumumab, n=1), gastric ulcer hemorrhage (placebo, n=1). No neutralizing antibodies were observed for either ganitumab or rilotumumab. Efficacy is shown in the table. Ganitumab and rilotumumab combined with chemotherapy showed comparable exposures as those under monotherapy and did not affect the pharmacokinetics of chemotherapy.
[a]Adjusted for baseline lactate dehydrogenase levels and stratification factors. CI=confidence interval; HR=hazard ratio.
Ganitumab (n=62) Rilotumumab (n=62) Placebo (n=61) OS Median (95% CI) months 10.7 (8.1–14.1) 12.2 (8.8–14.6) 10.8 (9.4–11.9) Adjusted HR[a] (95% CI) 1.01 (0.67–1.52) 0.91 (0.60–1.39) PFS Median (95% CI) months 5.5 (4.4–5.7) 5.4 (4.4–5.7) 5.4 (4.6–5.8) Adjusted HR[a] (95% CI) 1.03 (0.70–1.52) 1.03 (0.69–1.52) Objective Response Complete response, n (%) 0 (0) 2 (3) 1 (2) Partial response, n (%) 39 (63) 40 (65) 35 (57) Stable disease, n (%) 13 (21) 12 (19) 16 (26)
In this study of chemonaïve patients with extensive-stage SCLC, the combination of ganitumab or rilotumumab with CE or PE was tolerable; no unexpected toxicities were observed. There were no meaningful improvements in OS, PFS, or ORR with either combination. Survival analyses in biomarker and pharmacokinetic subgroups are ongoing.
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