What is the mechanism of action of this treatment?

Common treatments for colorectal cancer include targeted therapies and chemotherapeutics. Targeted therapies, such as those inhibiting the RAS/MAPK pathway (e.g., DCC-3116), work by blocking specific molecules involved in tumor growth and survival, making them particularly effective for tumors with specific genetic mutations. Chemotherapeutics like fluoropyrimidines and oxaliplatin-based regimens (e.g., FOLFOX) interfere with DNA replication and cell division, leading to cancer cell death. Understanding these mechanisms is crucial for colorectal cancer patients as it allows for personalized treatment plans that can improve efficacy and reduce unnecessary side effects.

What side effects are associated with this type of intervention?

Common treatments for colorectal cancer, particularly those targeting RAS/MAPK pathway mutations, include MEK inhibitors like selumetinib. Known side effects of these treatments can include rash, nausea, vomiting, diarrhea, and fatigue. In some cases, more severe toxicities such as grade 3 acneiform rash and grade 4 hypomagnesemia have been observed. General side effects of colorectal cancer treatments, including chemotherapy regimens like FOLFOXIRI, can also involve diarrhea, rash, and other gastrointestinal issues. Chronic diarrhea and bowel dysfunction are notable long-term effects that significantly impact quality of life.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of colorectal cancer, particularly those targeting the RAS/MAPK pathway. Cetuximab and panitumumab are monoclonal antibodies that target the epidermal growth factor receptor (EGFR) and are used in patients with wild-type KRAS metastatic colorectal cancer. Additionally, the combination of encorafenib (a BRAF inhibitor) with cetuximab has been approved for patients with BRAF V600E-mutant metastatic colorectal cancer. These treatments are part of a broader strategy to target specific genetic mutations within the RAS/MAPK pathway, similar to the investigational drug DCC-3116.

What other types of research exist?

Promising alternatives to DCC-3116 for colorectal cancer patients include sotorasib and adagrasib, which target KRAS G12C mutations. Additionally, the combination of sorafenib and irinotecan (NEXIRI) has shown potential in patients with RAS-mutated metastatic colorectal cancer who have progressed after standard therapies.

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MAPK Pathway Inhibitor

DCC-3116 for Solid Tumors

Phase 1 & 2

Recruiting

Research Sponsored by Deciphera Pharmaceuticals LLC

Eligibility Criteria Checklist

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

Must have

Participants enrolled in the DCC-3116 and sotorasib cohort (Cohort D) must have a KRAS G12C mutation.

Have not received prior MEK inhibitor therapy.

Must not have

For participants receiving DCC-3116 and trametinib combination or DCC-3116 and binimetinib combination: previous treatment with trametinib or binimetinib that resulted in treatment discontinuation due to intolerability as a result of an adverse event (AE) that was considered related to trametinib or binimetinib.

For participants receiving DCC-3116 and sotorasib combination in Dose Escalation Part 1: previous treatment with sotorasib that resulted in treatment discontinuation due to intolerability as a result of an adverse event (AE) that was considered related to sotorasib.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 24 months

Awards & highlights

Approved for 5 Other Conditions

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial tests a new drug, DCC-3116, alone and with other drugs, in patients with advanced cancers that have specific genetic mutations. The drug works by blocking a pathway that helps cancer cells grow.

Who is the study for?

Adults with advanced solid tumors having specific mutations (RAS/MAPK pathway) who've had certain prior treatments can join. They need good organ function, an ECOG score of 0-2, and must not be pregnant or breastfeeding. Contraception is required for both men and women.

What is being tested?

The trial tests DCC-3116 alone or with trametinib, binimetinib, or sotorasib in two phases: dose escalation to find safe amounts and expansion to see effects on different cancers like colorectal cancer and melanoma.

What are the potential side effects?

Potential side effects include typical reactions from targeted cancer therapies such as fatigue, digestive issues, skin rash, liver enzyme changes. Specific side effect profiles will depend on the drug combination received.

Eligibility Criteria

Inclusion Criteria

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

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My cancer has a KRAS G12C mutation.

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I have never been treated with MEK inhibitors.

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My lung cancer has a specific KRAS G12C mutation.

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My pancreatic cancer has a KRAS mutation.

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I've had 1 or 2 treatments for advanced cancer that included drugs to boost my immune system.

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My lung cancer has a specific genetic mutation.

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I have a BRAF V600 mutation and have tried treatments that are known to work.

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I have had 1 to 3 treatments for my advanced cancer.

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I am mostly active and can care for myself.

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My advanced cancer has a confirmed RAS, NF1, or RAF mutation.

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I have had at least 2 treatments for my advanced cancer.

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My melanoma has an NRAS mutation.

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My colorectal cancer has a specific genetic mutation.

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I have had 2 to 4 treatments for my advanced cancer.

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I am 18 years old or older.

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I have had one treatment for my cancer after it spread.

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My NSCLC has a KRAS G12C mutation.

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I have been diagnosed with Pancreatic Ductal Adenocarcinoma.

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My cancer has worsened despite treatment, and I've had at least one type of cancer therapy.

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I have never been treated with sotorasib or similar drugs.

Exclusion Criteria

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

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I stopped taking trametinib or binimetinib due to side effects.

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I stopped taking sotorasib because of its side effects.

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I am receiving or have received treatment for bone disease.

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I have had blood clots in my arteries.

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I have not had major surgery in the last 4 weeks and my surgical wounds are healed.

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My heart's electrical activity test shows prolonged QT intervals.

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I do not have severe heart problems or recent heart attacks.

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I am not pregnant or breastfeeding.

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I have had blood clots in my veins.

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I have a condition that prevents my body from absorbing nutrients properly.

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I do not have active hepatitis B or C, and I am not on any prohibited medications.

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I haven't had any AIDS-related infections in the past year.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 24 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence of Adverse Events

Maximum tolerated dose (MTD) (Escalation Phase)

Objective response rate (ORR) (Expansion Phase)

Secondary study objectives

Area under the concentration-time curve (AUC)

Disease Control Rate (DCR)

Duration of response (DoR)

+5 more

Awards & Highlights

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

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

Trial Design

6Treatment groups

Experimental Treatment

Group I: Expansion Cohorts 1, 2, 3 and 4 (Part 2)Experimental Treatment1 Intervention

Expansion Cohorts 1, 2, 3 and 4 DCC-3116 combinations will not open for enrollment.

Group II: Expansion Cohort 5 (Part 2)Experimental Treatment2 Interventions

DCC-3116 tablets orally given in combination with sotorasib in 28-day cycles to evaluate safety and preliminary efficacy of participants with NSCLC (with a documented mutation in KRAS G12C).

Group III: Dose Escalation (Part 1, Cohort D Combination)Experimental Treatment2 Interventions

Upon determination of the RP2D/MTD single agent, DCC-3116 will be dosed in combination with sotorasib.

Group IV: Dose Escalation (Part 1, Cohort C Combination)Experimental Treatment2 Interventions

Upon determination of the RP2D/MTD single agent, DCC-3116 will be dosed in combination with binimetinib. Escalation Cohort C combination closed on January 8, 2024.

Group V: Dose Escalation (Part 1, Cohort B Combination)Experimental Treatment2 Interventions

Upon determination of the RP2D/MTD single agent, DCC-3116 will be dosed in combination with trametinib. Escalation Cohort B combination closed on January 8, 2024.

Group VI: Dose Escalation (Part 1, Cohort A Monotherapy)Experimental Treatment1 Intervention

DCC-3116 tablets in escalating dose cohorts given orally twice daily (BID) in 28-day cycles as monotherapy (single agent). If no DLT in 3 participants or 1 DLT/6 participants is observed, dose escalation may continue to the next planned dose cohort.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Trametinib

2014

Completed Phase 2

~1630

Binimetinib

FDA approved

Sotorasib

FDA approved

0 / 32Eligibility 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 colorectal cancer include targeted therapies and chemotherapeutics. Targeted therapies, such as those inhibiting the RAS/MAPK pathway (e.g., DCC-3116), work by blocking specific molecules involved in tumor growth and survival, making them particularly effective for tumors with specific genetic mutations. Chemotherapeutics like fluoropyrimidines and oxaliplatin-based regimens (e.g., FOLFOX) interfere with DNA replication and cell division, leading to cancer cell death. Understanding these mechanisms is crucial for colorectal cancer patients as it allows for personalized treatment plans that can improve efficacy and reduce unnecessary side effects.

Enhanced toxicity to chemoradiation in a patient with Anti-Jo-1-antisynthetase syndrome.Therapeutic approaches for relapsed/refractory adult acute lymphoblastic leukemia (ALL), a review on monoclonal antibodies and targeted therapies.Impact of molecular tumour board discussion on targeted therapy allocation in advanced prostate cancer.