What side effects are associated with this type of intervention?

Common treatments for pancreatic cancer, including RAF/MEK inhibitors like Avutometinib (VS-6766) and FAK inhibitors like Defactinib, often result in side effects such as fatigue, gastrointestinal symptoms (nausea, vomiting, diarrhea), and skin issues (rash, acne). Chemotherapy agents like gemcitabine and nab-paclitaxel, frequently used in pancreatic cancer treatment, can cause additional side effects including myelosuppression (leading to anemia, neutropenia, and thrombocytopenia), peripheral neuropathy, and increased risk of infections. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for pancreatic cancer, primarily focusing on chemotherapy agents such as gemcitabine and nab-paclitaxel. While there are no specific FDA approvals for RAF/MEK inhibitors or FAK inhibitors in pancreatic cancer, investigational studies like the one involving Avutometinib (VS-6766) and Defactinib are exploring these pathways. These studies aim to target the molecular mechanisms involved in cancer cell growth and survival, potentially offering new therapeutic options for patients with pancreatic ductal adenocarcinoma.

What other types of research exist?

Promising novel alternatives for pancreatic cancer treatment in 2024 include: <ol> <li>Immunotherapy agents such as pembrolizumab (Keytruda) for patients with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR).</li> <li></li> </ol> PARP inhibitors like olaparib (Lynparza) for patients with BRCA1/2 mutations. 3. Targeted therapies such as larotrectinib (Vitrakvi) for tumors with NTRK gene fusions. 4. New combinations of chemotherapy agents, including FOLFIRINOX (a combination of folinic acid, fluorouracil, irinotecan, and oxaliplatin) and gemcitabine plus nab-paclitaxel. 5. Emerging kinase inhibitors and other targeted agents under investigation in clinical trials.

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Kinase Inhibitor

Avutometinib + Defactinib + Chemotherapy for Pancreatic Cancer (RAMP205 Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Verastem, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologic or cytologic evidence of metastatic pancreatic ductal adenocarcinoma

An Eastern Cooperative Group (ECOG) performance status ≤ 1

Must not have

Patients with pancreatic neuroendocrine tumors

Prior or concomitant treatment for metastatic pancreatic ductal adenocarcinoma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment combining two experimental drugs with two existing treatments for patients with newly diagnosed pancreatic cancer. The goal is to see if this combination can safely and effectively stop cancer growth and kill cancer cells. The study focuses on patients who have not yet received any treatment. One of the existing treatments used in the trial has been important in pancreatic cancer treatment but offers only modest improvements in symptoms and survival.

Who is the study for?

This trial is for adults with untreated metastatic pancreatic ductal adenocarcinoma (PDAC), who are in good physical condition (ECOG ≤ 1) and have measurable disease. They must have proper organ and heart function, and agree to use effective contraception. Excluded are those with neuroendocrine tumors, prior PDAC treatments, RAS/MAPK or FAK inhibitor history, other recent malignancies unless cured, major surgery within the last month, severe heart/lung diseases, eye disorders, lung conditions like fibrosis or edema, or a recent SARS-CoV-2 infection.

What is being tested?

The study tests the safety and effectiveness of avutometinib (VS-6766) combined with defactinib alongside standard chemotherapy drugs gemcitabine and nab-paclitaxel in patients who haven't been treated before for their pancreatic cancer. The goal is to see if this combination works better than current treatments.

What are the potential side effects?

Potential side effects may include reactions related to immune system activation such as inflammation in various organs; typical chemotherapy-related issues like nausea, fatigue; blood cell count changes increasing infection risk; possible cardiac complications due to drug interactions; skin reactions requiring systemic treatment.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is a type of pancreatic cancer that has spread.

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I am fully active or can carry out light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a pancreatic neuroendocrine tumor.

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I have received treatment for advanced pancreatic cancer.

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I have an eye condition.

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I have not had major surgery in the last 4 weeks.

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I have heart disease or severe lung problems.

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I have not been treated with RAS/MAPK or FAK inhibitors.

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I have severe lung conditions like interstitial lung disease or pulmonary fibrosis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Part A: To determine RP2D for avutometinib (VS-6766) and defactinib in combination gemcitabine and nab-paclitaxel

To determine the efficacy of the RP2D identified in Part A

Secondary study objectives

Disease Control Rate (DCR)

Duration of Response (DOR)

Frequency and severity adverse events (AEs) and Serious Adverse Events (SAEs)

+6 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinib RP2DExperimental Treatment1 Intervention

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

Group II: Gemcitabine + nab-paclitaxel + avutometinib (VS-6766) + defactinibExperimental Treatment1 Intervention

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

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for pancreatic cancer include chemotherapy, targeted therapies, and investigational agents like Avutometinib (VS-6766) and Defactinib. Chemotherapy agents such as gemcitabine and nab-paclitaxel work by interfering with DNA replication, thereby inhibiting cancer cell growth. Targeted therapies, including RAF/MEK inhibitors like Avutometinib, block specific signaling pathways that promote tumor growth and survival. FAK inhibitors like Defactinib disrupt the focal adhesion kinase pathway, which is involved in cancer cell adhesion, migration, and survival. These targeted approaches are crucial for pancreatic cancer patients as they offer more precise treatment options that can potentially improve outcomes and reduce side effects compared to traditional chemotherapy.