NewLink Genetics Corporation has launched an open-label, randomized, multi-institutional adaptive design phase IIB/III study to evaluate efficacy of its tergenpumatucel-L (HyperAcute-Lung) product candidate in patients with progressive or relapsed Stage-IIIB/IV non-small cell lung cancer (NSCLC).

The phase II B portion of the study will evaluate two dosing schedules for tergenpumatucel-L versus docetaxel and the phase III portion of the study will further assess efficacy of the selected dose against docetaxel. The primary endpoint of the study will be to evaluate survival in second-line therapy for patients with advanced non-small cell (stage IIIB/IV) lung cancer. Secondary objectives include progression free survival, evaluation of tumor response, and immunological response in treated patients.

"We are pleased to move another promising HyperAcute product candidate with encouraging survival data from phase II into advanced-stage studies," commented Dr Charles Link, chairman and CEO of NewLink. Link further added, "NSCLC remains the leading cause of cancer death in the United States."

"Immunotherapies are emerging as one of the most promising next treatment paradigms for cancer patients by allowing the patient's immune system to fight their disease without significant new toxicities. We are excited to participate in this advanced study to evaluate NewLink's innovative HyperAcute Lung immunotherapy in NSCLC," said principal investigator of the study Dr Ramaswamy Govindan, Professor of Medicine, co-director Section of Medical Oncology at the Alvin J Siteman Cancer Centre, Washington Univ School of Medicine, St. Louis, MO.

"This trial design is based on phase II non-small cell lung cancer data presented at the recent ASCO meeting demonstrating 11.2 months median survival in 2nd and third line patients who failed prior treatment. Our correlative immunological data showing 21.9 vs. seven months survival in certain patients capable of  generating IFN-gamma responses versus patients who did not mount this response, suggest patients with the best immune responses may have significantly greater long term overall survival. If these types of data can be confirmed in the new larger, randomized study an important novel therapy will be made available for patients with very limited options. We are delighted to be one of the lead centres,” commented principal investigator for the phase II study and Co-PI for the phase III study Dr John C Morris, Professor of Medicine, Director of Experimental Therapeutics, Thoracic Cancer and Head & Neck Cancer Programmes at Univ of Cincinnati, Cincinnati, Ohio.

Although a number of therapies have been approved in lung cancer, the prognoses for patients remain poor. "This study is designed to test the hypothesis that patients treated with HyperAcute immunotherapies may be sensitized to subsequent treatments with chemotherapy while also evaluating whether survival benefits observed in our phase II study can be reproduced in a large controlled phase III study," commented Dr Nick Vahanian, president, chief medical officer, NewLink Genetics.

This phase II B/III study will enroll patients having a better baseline immune system status relative to the patient population in the earlier phase II study. In order to be eligible for the study, patients must have Stage IIIB or Stage IV recurrent or treatment refractory non-small cell lung cancer with good performance status (ECOG < 2) and no more than one prior chemotherapy failure. A lymphocyte count of > /= 1000/µL, platelets > /= 100,000/µL, hemoglobin > 10.0 gm/dL, albumin > /= 3.0 gm/dL and acceptable hepatic and renal function are required for enrollment.

Two hundred forty (240) patients will be randomized (2:1:1) to receive: Arm 1: Docetaxel 75 mg/m2 intravenously given every 3 weeks for 4 doses; Arm 2a: Tergenpumatucel-L at 300 million cells given by intradermal injection weekly for 11 weeks then every 2 months for 5 additional doses (up to a total of 16 immunizations); Arm 2b: Tergenpumatucel-L at 300 million cells given by intradermal injection every 2 weeks for 6 doses and then every month for 10 additional doses (up to a total of 16 immunizations).

In the phase III portion of the study, patients will be randomized (1:1) to receive either docetaxel or tergenpumatucel-L at the dose level that was selected in the phase II B portion of the study. At the planned interim analysis a sample size re-estimation will be performed that will determine the final enrollment numbers for the trial.