UAB 0601

TITLE:            UAB 0601 - A Phase 2 Double-Blind, Placebo-Controlled, Multi-Center Adjuvant Trial of the Efficacy, Immunogenicity, and Safety of GI-4000, an Inactivated Recombinant Saccharomyces cerevisiae Expressing Mutant Ras Protein Combined with a Gemcitabine Regimen Versus a Gemcitabine Regimen with Placebo, in Patients with Post-Resection R0/R1 Pancreatic Cancer with Tumor Sequence Confirmation of Ras Mutations 

SPONSORS:  GlobeImmune, Inc.

INVESTIGATOR:     Pablo Arnoletti, M.D.

PRIMARY OBJECTIVE 

To evaluate the efficacy of weekly followed by monthly doses of GI-4000 in combination with adjuvant gemcitabine versus adjuvant gemcitabine with placebo in post-resection pancreas cancer subjects, as measured by recurrence-free survival at 15 months (primary efficacy endpoint).

STUDY POPULATION

The study population will consist of patients with resectable pancreas cancer who have a product-related mutation in Ras (G12V, G12C, G12D, Q61L, or Q61R) and an R0 or R1 resection by Whipple or pylorus-preserving Whipple.

STUDY DRUG

GI-4000 is three separate products from the GI-4000 series, GI-4014, GI-4015, and GI-4016. Each of these is a recombinant, heat-inactivated S. cerevisiae engineered to express one of three mutated Ras oncoproteins.

STUDY DESIGN

This is a double-blind, placebo-controlled, multi-center, adjuvant trial evaluating weekly followed by monthly doses of GI-4000 in combination with a gemcitabine regimen versus a gemcitabine regimen alone in patients with resected pancreatic cancer (R0/R1). R0/R1 post-resection patients will be randomized in a 1:1 ratio to either GI-4000 combined with gemcitabine or placebo combined with gemcitabine. Patients will be dosed with GI-4000 40YU or placebo with three weekly doses starting between 21 and 35 days after resection (study visits Day 1, 8, 15) and gemcitabine 1000mg/m² intravenous infusion starting on study visit Day 24 (between six and eight weeks after resection). Monthly doses of GI-4000 will be administered after initiation of the gemcitabine regimen and will be sequenced to coincide with the monthly chemotherapy holiday (Day 21 of the 28-day gemcitabine cycle).

INCLUSION CRITERIA

Key inclusion criteria include the following:

1. Subjects must have resectable pancreas cancer, ductal adenocarcinoma type, with post-resection confirmation of non-metastatic disease
2. Confirmed product-related mutation in Ras from tumor sample
3. ECOG performance status of ≤ 2 prior to randomization
4. Post-operative confirmed R0 or R1 resection status
5. Negative scratch test (immediate hypersensitivity, IgE mediated) to S. cerevisiae

EXCLUSION CRITERIA

Key exclusion criteria include the following:

1. Non-resectable pancreatic cancer or histologic types other than ductal adenocarcinoma (e.g., papillary cystoadenocarcinoma, mucinous adenocarcinoma)
2. Prior chemotherapy, radiation therapy, targeted therapy, or immunotherapy for pancreatic cancer
3. History of another cancer within the last five years with the exception of localized basal or squamous cell carcinoma of the skin, Stage 1A cervical cancer, or melanoma in situ
4. History of Crohn's disease or ulcerative colitis
5. History of major organ transplantation
6. Concurrent and chronic therapy with corticosteroids (greater than 10mg per day of prednisone or an equipotent dose of another corticosteroid) or any other immunosuppressive drugs. Use of Dexamethasone as an antiemetic during gemcitabine dosing will be permitted during the trial.
7. Known hypersensitivity to gemcitabine

ADDITIONAL INFORMATION

Contact:   Dayle Craig, R.N.

               Telephone: 205-975-8080

                E-mail: dayle.craig@ccc.uab.edu