Potential chemo-sensitization effect of tergenpumatucel-L immunotherapy in treated patients with advanced non-small cell lung cancer (NSCLC).

Abstract

8094 Background: Lung cancer is the leading cause of cancer-related mortality. Tumor progression after initial chemotherapy has a poor prognosis. A major obstacle is chemo-resistance, thus targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents with limited toxicities are needed. We report that tergenpumatucel-L (HyperAcute-Lung immunotherapy, HAL) shows signs of chemo-sensitization to follow-up treatment after progression in immunized patients. This drug exploits a potent innate immune mechanism that normally functions to destroy cells expressing a common xenoantigen (αGal). HAL immunotherapy consists of injecting patients with genetically modified allogeneic NSCLC cells bearing αGal moieties on their cell surface. Methods: This phase II study included 28 patients with metastatic or recurrent NSCLC, age ≥18, ECOG PS ≤2, ≤2 prior systemic therapies. Trial objectives were response rate, safety and immunogenicity. Patients received 300 x 106HAL cells q2wks x 8 doses. Adverse events were assessed using CTCAE v3. Immunogenicity was assessed by changes in serum anti-αGal titers and IFN-γ response. Patients progressing on study trial (n=16) received follow up chemotherapy. Response was evaluated using RECIST criteria. Results: Twenty-eight (28) patients were evaluable for response and 16 progressing patients received salvage chemotherapy. Median overall survival (OS) was 11.3 months (95% CI 3.8-21.9). Eight of 28 patients demonstrated stable disease (SD) ≥16 wks including one patient that progressed and later regressed to survive >50 months. Fifty six percent (9/16) of the progressing patients receiving follow up chemotherapy showed a response. Five (31%) achieved a PR and 25% (4/16) had SD after initial progression during the trial suggesting a chemo-sensitization effect of tergenpumatucel-L. Conclusions: HAL immunotherapy is safe and feasible. The median OS compared favorably to that reported in patients receiving 2nd line chemotherapy for relapsed or advanced NSCLC. The potential chemo-sensitization effect of tergenpumatucel-L is highly encouraging and currently being studied in a phase IIB/III trial. Clinical trial information: NCT00073398.