Author of

• 11818

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  P2.13 - Poster Session 2 - SCLC (ID 201)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11820

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    P2.13-002 - Randomized Phase II Study of Single Agent OSI-906, an Oral, Small Molecule, Tyrosine Kinase Inhibitor (TKI) of the Insulin Growth Factor-1 Receptor (IGF-1R) Versus Topotecan for the Treatment of Patients with Relapsed Small Cell Lung Cancer (SCLC) (ID 920)

    09:30 - 09:30  |  Author(s): T. Owonikoko
    • Abstract

    Background
    SCLC typically presents with advanced (extensive stage) disease. Despite an initial response to chemotherapy, they all relapse and rarely survive beyond 2 years. Treatment of relapsed SCLC is limited (topotecan) and dependent on the response to initial chemotherapy (sensitive vs. refractory relapse). Downstream activation of PI3K-AKT, through IGF-1R pathway signaling plays a role in both, growth/survival and resistance to chemotherapy in SCLC. Growth inhibition and chemosensitization with IGF-1R inhibitors correlates with the PI3K-AKT inhibitory signaling and suggests AKT activation as a potential biomarker. OSI-906, is a well tolerated oral, small molecule, potent inhibitor of IGF-1R

    Methods
    A phase II randomized study comparing the efficacy of OSI-906 vs topotecan in patients with rSCLC is currently being conducted. Primary endpoint is PFS, summarized with the K-M method. An increase in median PFS from 2.5 to 4.175 months (in the experimental arm B) is proposed. A total of 95 patients are planned. Biomarkers of IGF-1R inhibition are explored in plasma, PBMC and using Radiomics. Eligible patients must have proven rSCLC, platinum sensitive (sen) or resistant (res) disease, ECOG PS 0-2 and adequate hematologic, renal and hepatic function. Fasting glucose <160 mg/dl, QTc < 450 msec and measurable disease by RECIST v1.1 are required. Pregnant, breast-feeding, diabetic and cirrhotic patients as well as those taking insulin/insulinotropic agents are excluded. Patients are randomized (2:1) to the experimental arm (B): OSI-906, 150 mg PO BID, until progression or to the standard arm (A): topotecan, 1.5 mg/m[2] IV daily x5 OR 2.3 mg/m[2] PO daily x5, for 4 cycles. Crossover to OSI-906 is allowed.

    Results
    Figure 1 Thirty-three patients have been enrolled; A=10 (res=6, PS 2=2) and B=23 (res=15, PS 2=4). M/F= 13/20; ECOG PS 0/1/2 = 8/19/6. Platinum sen/res = 12/21. Two patients were not treated (A/B = 1/1). Adverse events are described in Table 1. No responses have been observed. Only 2/6 and 1/15 patients in arms A and B respectively achieved SD at 6 weeks. Median PFS (A/B) was 2.1 (95% CI; 0.6, 3.6) and 1.3 (95% CI; 1.0, 1.4) months respectively (p = 0.0149). OS was not reached in arm A and 2.7 (95% CI; 1.5, …) months in arm B (p = 0.1716).

    Conclusion
    OSI-906 is safe in rSCLC patients. In our unselected, high risk population, efficacy in both arms, but particularly in arm B appears suboptimal. The study continues to accrue to reach the sample size and follow up time needed for more robust conclusions.