a study of eli-002 7p in subjects with kras/nras mutated solid tumors

Conditions: Pancreatic Ductal Adenocarcinoma; Colorectal Cancer; KRAS G12D; KRAS G12R; KRAS G12V; KRAS G12A; KRAS G12C; KRAS G12S; KRAS G13D; NRAS G12D; NRAS G12R; NRAS G12V; NRAS G12C; NRAS G12S

Summary: this is a phase 1/2 study to assess the safety and efficacy of eli-002 7p immunotherapy (a lipid-conjugated immune-stimulatory oligonucleotide \[amph-cpg-7909\] plus a mixture of lipid-conjugated peptide-based antigens \[amph-peptides 7p\]) as adjuvant treatment in subjects with solid tumors with mutated kras/nras. this study builds on the experience obtained with related product eli-002 2p, which was studied in protocol eli-002-001 under ind 26909.

the study consists of 3 phases: phase 1a, phase 1b, and phase 2. in phase 1a, seven amph modified kras and nras peptides, g12d, g12r, g12v, g12a, g12c, g12s, g13d (amph-peptides 7p) will be evaluated in combination with recommended phase 2 dose of amph-cpg-7909 (10.0mg). this amph-cpg-7909 dose will be evaluated with two amph-peptides 7p dose levels (1.4mg and 4.9mg) in 6 subjects per dose level. following enrollment of these 12 subjects, the independent data monitoring committee (idmc) will decide if another 6 subjects should be enrolled or if the dose can be determined for phase 1b and phase 2 portions of the study to be opened. if another 6 subjects are enrolled to phase 1a, the idmc will meet again to decide upon the dose for phase 1b and phase 2 prior to opening these portions of the study. in phase 1b, one dose expansion cohort of up to 17 colorectal cancer \[crc\] subjects may be added to evaluate for preliminary evidence of biomarker response, including circulating tumor deoxyribonucleic acid (ctdna) and/or serum tumor biomarker (such as ca19-9 and cea) reduction and clearance in kras and nras. in phase 2, an additional 135 pdac subjects will be randomized 2:1 (eli-002 7p versus observation) to further evaluate antitumor activity. subjects randomized to eli-002 7p will receive subcutaneous (sc) injections of eli-002 7p during immunization and booster periods. subjects randomized to observation will have the same safety and efficacy evaluations and will follow the same assessment schedule as subjects randomized to eli-002 7p but will not receive study treatment. subjects randomized to observation will be able to elect to cross-over to eli-002 7p treatment in the event of confirmed disease progression.

Eligibility criteria:
inclusion criteria: * kras/nras mutated (g12d, g12r, g12v, g12a, g12c, g12s, g13d) solid tumor * phase 1 only: positive for circulating tumor dna and/or elevated serum tumor biomarkers (such as ca19-9 and cea) despite prior standard therapy including surgery and chemotherapy/radiation therapy where applicable * screening ct is negative for recurrent disease * eastern cooperative oncology group (ecog) performance status of 0 or 1 exclusion criteria: * presence of tumor mutations where specific therapy is approved * known brain metastases * use of immunosuppressive drugs

Keywords: kirsten rat sarcoma (kras) neuroblastoma ras viral oncogene homolog (nras) pancreatic ductal adenocarcinoma (pdac) colorectal cancer (crc) colon cancer rectal cancer immunotherapy vaccine therapy adjuvant therapy serum tumor biomarker carbohydrate antigen 19-9 (ca19-9) carcinoembryonic antigen (cea) circulating tumor dna (ctdna)