Study of Avutometinib (VS-6766) +Defactinib With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

This study will assess the safety and efficacy of avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel in patients with Pancreatic Ductal Adenocarcinoma (PDAC) who have been previously untreated.

Detailed description public domain (ClinicalTrials.gov)

This is a multicenter, non-randomized, open-label Phase 1/2 study designed to evaluate safety, tolerability and efficacy of avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel in patients previously untreated metastatic Pancreatic Ductal Adenocarcinoma (PDAC).

Intervention public domain (ClinicalTrials.gov)

Drug: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel. The RP2D of avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel determined in Part A will be used in Part B dose expansion.

Arm public domain (ClinicalTrials.gov)

Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib (experimental): To determine the recommended phase 2 dose (RP2D) for gemcitabine Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib in patients with untreated metastatic PDAC.

Arm public domain (ClinicalTrials.gov)

Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib RP2D (experimental): To determine the efficacy of the RP2D identified in Part A in untreated metastatic PDAC patients

Primary outcome public domain (ClinicalTrials.gov)

Part A: To determine RP2D for avutometinib (VS-6766) and defactinib in combination gemcitabine and nab-paclitaxel. Assessment of Dose-limiting toxicities (DLTs) Time frame: 28 days.

Primary outcome public domain (ClinicalTrials.gov)

To determine the efficacy of the RP2D identified in Part A. Confirmed overall response rate (ORR) (partial response \[PR\] + complete response \[CR\] defined according to Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\]) Time frame: 6 months.

Secondary outcome public domain (ClinicalTrials.gov)

Duration of Response (DOR). Time frame: 24 months.

Secondary outcome public domain (ClinicalTrials.gov)

Disease Control Rate (DCR). Time frame: 24 months.

Secondary outcome public domain (ClinicalTrials.gov)

Progression Free Survival (PFS). Time frame: 24 months.

Secondary outcome public domain (ClinicalTrials.gov)

Overall Survival (OS). Time frame: Up to 5 years.

Secondary outcome public domain (ClinicalTrials.gov)

Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, Tmax. Time frame: 10 weeks.

Secondary outcome public domain (ClinicalTrials.gov)

Plasma Pharmacokinetics (PK) of avutometinib (VS-6766) and Defactinib and relevant metabolites, AUC. Time frame: 10 Weeks.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: * Male or female subjects ≥ 18 years of age * Histologic or cytologic evidence of metastatic pancreatic ductal adenocarcinoma. * An Eastern Cooperative Group (ECOG) performance status ≤ 1 * Measurable disease according to RECIST 1.1 * Adequate organ function * Adequate cardiac function * Agreement to use highly effective method of contraceptive Exclusion Criteria: * Patients with pancreatic neuroendocrine tumors * Prior or concomitant treatment for metastatic pancreatic ductal adenocarcinoma * Prior treatment with inhibitors of the RAS /MAPK pathway \[e.g. MEK inhibitors\] or inhibitors of FAK * History of prior malignancy, with the exception of curatively treated malignancies * Major surgery within 4 weeks (excluding placement of vascular access) * Concurrent heart disease or severe obstructive pulmonary disease * Concurrent ocular disorders * Active skin disorder that has required systemic therapy within the past 1 year * Patients with interstitial lung disease or pulmonary fibrosis or severe lung disease, pulmonary edema, and adult respiratory distress syndrome * Known SARS-Cov2 infection ≤28 days prior to first dose of study therapy

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 40 participants (estimated).