Study of Avutometinib (VS-6766) +Defactinib With Gemcitabine and Nab-paclitaxel in Patients With Pancreatic Cancer (RAMP205)

Verastem

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Metastatic Cancer; KRAS Activating Mutation; Neoplasms Pancreatic; Pancreas Cancer; Malignant Neoplasm of Pancreas

Treatments: Drug: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT05669482

VS-6766-205

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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40 participants in 2 patient groups

Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib

Experimental group

Description:

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

Treatment:

Drug: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel

Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib RP2D

Experimental group

Description:

To determine the efficacy of the RP2D identified in Part A in untreated metastatic PDAC patients

Treatment:

Drug: avutometinib (VS-6766) and defactinib in combination with gemcitabine and nab-paclitaxel