Date: 2016-06-09
Type of information: Publication of results in a medical journal
phase: 1b/2
Announcement: publication of results in The Lancet
Company: Eli Lilly (USA - IN)
Product: olaratumab
Action
mechanism: monoclonal antibody. Olaratumab is a fully human IgG1 monoclonal antibody designed to bind to the platelet-derived growth factor receptor alpha (PDGFR alpha) and block PDGFR alpha activation. PDGFR alpha is expressed in a variety of tumor types, plays an important role in cancer growth and metastasis, and modulates stromal- and angiogenesis-driven mechanisms of cancer growth. PDGFR alpha and its ligands are coexpressed in many tumor types, and PDGFR alpha overexpression is associated with increased metastasis.
Disease: advanced soft tissue sarcoma (STS) not amenable to curative treatment with radiotherapy or surgery
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On June 9, 2016, Eli Lilly announced that The Lancet published detailed results from a Phase 2 study evaluating the efficacy and safety of olaratumab, in combination with doxorubicin chemotherapy in patients with advanced soft tissue sarcoma (STS) not amenable to curative treatment with radiotherapy or surgery. The study met its primary endpoint of progression-free survival (PFS) and showed a statistically significant improvement in overall survival. The open-label, randomized Phase 1b/2 study, JGDG, compared olaratumab in combination with doxorubicin chemotherapy to the control arm of doxorubicin alone in patients with unresectable, advanced STS not amenable to curative treatment with surgery or radiotherapy. After confirmation of safety in the Phase 1b portion of the study, 133 doxorubicin-naïve patients were randomized 1:1 in the Phase 2 portion of the study. A total of 66 patients were treated on the olaratumab-doxorubicin arm, and 67 on the placebo-doxorubicin arm. The primary endpoint of the study was PFS. Key secondary endpoints included OS and objective response rate (ORR). Randomization was balanced by ECOG performance status, histological tumor type, PDGFR expression and previous lines of treatment. Patients treated on the olaratumab and doxorubicin arm achieved 6.6 months of median PFS compared to 4.1 months on the placebo and doxorubicin arm (stratified hazard ratio [HR], 95 percent confidence interval [CI]: 0.672 [0.442?1.021]; p=0.0615). The investigator-assessed PFS was confirmed by independent review (HR=0.670; 95 percent CI: [0.04-1.12]; p=0.1208) with a median PFS of 8.2 months vs. 4.4 months. OS was statistically significant, with patients treated on the olaratumab and doxorubicin arm having achieved a median OS of 26.5 months (95 percent CI, 20.9?31.7) compared to 14.7 months (95 percent CI, 9.2?17.1) with doxorubicin (stratified HR, 0.463; 95 percent CI, 0.301?0.710; p=0.0003). The ORR was 18.2 percent (95 percent CI; [9.8-29.6]) with olaratumab plus doxorubicin and 11.9 percent (95 percent CI: [5.3-22.2]) with doxorubicin (p=0.3421). The most common (greater than 5 percent incidence) grade 3 or higher adverse events identified in the study were neutropenia (53.2 percent on the olaratumab combination arm vs. 32.3 percent on the placebo plus doxorubicin arm), anemia (12.5 percent vs. 9.2 percent) fatigue (9.4 percent vs. 3.1 percent) and musculoskeletal pain (8 percent vs. 2 percent). There were no increases in febrile neutropenia (12.5 percent on the olaratumab-doxorubicin arm vs. 13.8 percent on the placebo-doxorubicin arm), infections (7.8 percent vs. 10.8 percent) and patient discontinuations (13 percent vs. 19 percent). Grade 3 or higher infusion-related reactions occurred in 3 percent of patients on the olaratumab-doxorubicin arm vs. 0 percent on the placebo-doxorubicin arm. Lilly has submitted the results of this study to the FDA and European Medicines Agency (EMA) for regulatory review. The FDA recently granted Lilly Priority Review status for olaratumab. Lilly also has received additional designations for olaratumab from the FDA, including Breakthrough Therapy, Fast Track and Orphan Drug, for this indication. Additionally, the EMA is currently reviewing olaratumab under an accelerated assessment schedule.
