Study of Inlexisertib (DCC-3116) in Participants With RAS/MAPK Pathway Mutant Solid Tumors

NCT04892017 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: DCC-3116-01-0012022-501474-19-00
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 10

Brief Summary

This is a multicenter, open label, first in human (FIH) study of inlexisertib as monotherapy, and in combination with trametinib, binimetinib, or sotorasib in participants with advanced or metastatic solid tumors with RAS/MAPK pathway mutation. The study consists of 2 parts, a dose-escalation phase, and an expansion phase.

Conditions

Non-Small Cell Lung Cancer; Advanced Solid Tumor; Metastatic Solid Tumor

Keywords

KRAS G12C

Outcome Measures

Primary Outcomes (3)

• Incidence of Adverse Events

  Identify the observed adverse events, serious adverse events associated with inlexisertib as monotherapy and in combination with trametinib, binimetinib, or sotorasib.

  Approximately 24 months

• Maximum tolerated dose (MTD) (Escalation Phase)

  Identify the dose-limiting toxicities for each dose level tested and determine the maximum tolerated dose/recommended Phase 2 doses of inlexisertib as monotherapy and in combination with trametinib, binimetinib, or sotorasib.

  Approximately 18 months

• Objective response rate (ORR) (Expansion Phase)

  Proportion of participants who achieve CR or PR per RECIST v1.1.

  Approximately 24 months

Secondary Outcomes (8)

• Duration of response (DoR)

  Approximately 24 months

• Disease Control Rate (DCR)

  Approximately 24 months

• Time to response

  Approximately 24 months

• Progression-free survival (PFS)

  Approximately 24 months

• Maximum observed concentration (Cmax)

  Predose and up to 12 hours postdose

Study Arms (6)

Dose Escalation (Part 1, Cohort A Monotherapy)

EXPERIMENTAL

Inlexisertib 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.

Drug: Inlexisertib

Dose Escalation (Part 1, Cohort B Combination)

EXPERIMENTAL

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

Drug: Inlexisertib; Drug: Trametinib

Dose Escalation (Part 1, Cohort C Combination)

EXPERIMENTAL

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

Drug: Inlexisertib; Drug: Binimetinib

Dose Escalation (Part 1, Cohort D Combination)

EXPERIMENTAL

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

Drug: Inlexisertib; Drug: Sotorasib

Expansion Cohorts 1, 2, 3 and 4 (Part 2)

EXPERIMENTAL

Expansion Cohorts 1, 2, 3 and 4 inlexisertib combinations will not open for enrollment.

Drug: Inlexisertib

Expansion Cohort 5 (Part 2)

EXPERIMENTAL

Inlexisertib 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). Trial terminated prior to start of Part 2.

Drug: Inlexisertib; Drug: Sotorasib

Interventions

Inlexisertib DRUG

Oral Tablet Formulation

Also known as: DCC-3116

Dose Escalation (Part 1, Cohort A Monotherapy); Dose Escalation (Part 1, Cohort B Combination); Dose Escalation (Part 1, Cohort C Combination); Dose Escalation (Part 1, Cohort D Combination); Expansion Cohort 5 (Part 2); Expansion Cohorts 1, 2, 3 and 4 (Part 2)

Trametinib DRUG

Oral Tablet Formulation

Dose Escalation (Part 1, Cohort B Combination)

Binimetinib DRUG

Oral Tablet Formulation

Dose Escalation (Part 1, Cohort C Combination)

Sotorasib DRUG

Oral Tablet Formulation

Dose Escalation (Part 1, Cohort D Combination); Expansion Cohort 5 (Part 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants ≥18 years of age
• Dose Escalation Phase (Part 1):
• Escalation Cohort B combination with trametinib and Cohort C combination with binimetinib closed on January 8, 2024.
• Participants must have a pathologically confirmed diagnosis of an advanced or metastatic solid tumor with a documented RAS, NF1, or RAF mutations. A molecular pathology report documenting mutational status of RAS, NF1, or RAF must be available.
• Progressed despite standard therapies, and received at least 1 prior line of anticancer therapy.
• Participants with a documented mutation in BRAF V600E or V600K must have received approved treatments known to provide clinical benefit prior to study entry.
• Participants enrolled in the inlexisertib and sotorasib cohort (Cohort D) must have a KRAS G12C mutation.
• Dose Expansion Phase (Part 2):
• Expansion Cohorts 1, 2, 3 and 4 combinations will not open for enrollment.
• Cohort 5: Participants with KRAS G12C mutant NSCLC
• Pathologically confirmed NSCLC with a documented mutation in KRAS G12C.
• Received at least 1 prior line of systemic therapy in the advanced or metastatic setting.
• Have not received prior sotorasib or other KRAS G12C inhibitor therapy.
• Must provide a fresh tumor biopsy from a primary or metastatic cancer lesion if it can be biopsied with acceptable risk as determined by the Investigator.
• Must have at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST), v1.1

You may not qualify if:

• Must not have received the following within the specified time periods prior to the first dose of study drug:
• Prior therapies (anticancer or therapies given for other reasons) that are known strong or moderate inhibitors or inducers of CYP3A4 or P-glycoprotein (P-gp) including certain herbal medications (e.g., St. John's Wort): 14 days or 5× the half-life of the medication (whichever is longer)
• All other prior anticancer therapies or any therapy that is investigational for the participant's condition with a known safety and PK profile: 14 days or 5× the half-life of the medication (whichever is shorter)
• Investigational therapies with unknown safety and PK profile: 28 days. If there is enough data on the investigational therapy to assess the risk for drug-drug interactions and late toxicities of prior therapy as low, the Sponsor's Medical Monitor may approve a shorter washout of 14 days
• Grapefruit or grapefruit juice: 14 days
• Has a prior or concurrent malignancy that requires treatment or is expected to require treatment for active cancer during this study . Hormonal maintenance after treatment is allowed.
• Have not recovered from all toxicities from prior therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
• Presence or history of central nervous system (CNS) metastases or leptomeningeal disease, with some exceptions
• New York Heart Association Class III or IV heart disease, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia requiring therapy, uncontrolled hypertension, congestive heart failure, or myocardial infarction within 6 months prior to the first dose of study drug.
• Prolongation of the QT interval corrected by Fridericia's formula (QTcF) based on repeated demonstration of QTcF \>450 ms in males or \>470 ms in females at screening, or history of long QT syndrome.
• Left ventricular ejection fraction (LVEF) \<50% at Screening
• Systemic arterial thrombotic or embolic events within 6 months prior to the first dose of study drug
• Systemic venous thrombotic events within 1 month prior to the first dose of study drug
• Malabsorption syndrome
• Major surgery within 4 weeks of the first dose of study drug. All surgical wounds must be healed and free of infection or dehiscence before the first dose of the study drug.

Sponsors & Collaborators

• Deciphera Pharmaceuticals, LLC: lead

Study Sites (10)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Washington University Siteman Cancer Center

St Louis, Missouri, 63108, United States

Location

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901, United States

Location

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

NEXT Oncology

Austin, Texas, 78758, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

University of Wisconsin Clinical Science Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

trametinib; binimetinib; sotorasib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Team

  Deciphera Pharmaceuticals, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2021
• First Posted: May 19, 2021
• Study Start: June 15, 2021
• Primary Completion: March 30, 2026
• Study Completion: March 30, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-04

Locations

US (10)