ACTIVE_NOT_RECRUITING

A Phase 1/2 Study of Inlexisertib (DCC-3116) in Patients With RAS/MAPK Pathway Mutant Solid Tumors

Conditions

Non-Small Cell Lung Cancer Advanced Solid Tumor Metastatic Solid Tumor KRAS G12C

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a Phase 1/2, multicenter, open label, first in human (FIH) study of inlexisertib as monotherapy, and in combination with trametinib, binimetinib, or sotorasib in patients 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.

Official Title

A Phase 1/2, First-in-Human Study of DCC-3116 as Monotherapy and in Combination With RAS/MAPK Pathway Inhibitors in Patients With Advanced or Metastatic Solid Tumors With RAS/MAPK Pathway Mutations

Quick Facts

Study Start:2021-06-15

Study Completion:2028-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04892017

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Male or female participants ≥18 years of age 2. Dose Escalation Phase (Part 1): 1. 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. 2. 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. 3. Participants enrolled in the inlexisertib and sotorasib cohort (Cohort D) must have a KRAS G12C mutation. 3. Dose Expansion Phase (Part 2): * 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. 4. 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. 5. Must have at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST), v1.1 6. Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 (Dose Escalation) or 0 to 1 (Dose Expansion) at Screening 7. Adequate organ function and bone marrow function. 8. If a female of childbearing potential must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements. 9. Male participants must agree to follow contraception requirements. 10. Must provide signed consent to participate in the study and is willing to comply with study-specific procedures.	1. Must not have received the following within the specified time periods prior to the first dose of study drug: 1. 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) 2. 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) 3. 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 4. Grapefruit or grapefruit juice: 14 days 2. 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. 3. Have not recovered from all toxicities from prior therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). 4. Presence or history of central nervous system (CNS) metastases or leptomeningeal disease, with some exceptions 5. 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. 6. 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. 7. Left ventricular ejection fraction (LVEF) \<50% at Screening 8. Systemic arterial thrombotic or embolic events within 6 months prior to the first dose of study drug 9. Systemic venous thrombotic events within 1 month prior to the first dose of study drug 10. Malabsorption syndrome 11. 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. 12. Any other clinically significant comorbidities. 13. For participants receiving inlexisertib and trametinib combination or inlexisertib 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. 14. For participants receiving inlexisertib 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. 15. For participants receiving inlexisertib and sotorasib combination: Use of proton pump inhibitors (PPIs) and H2 receptor antagonists that cannot be discontinued 3 days prior to the start of study drug administration. 16. Known allergy or hypersensitivity to any component of the investigational drug products. 17. Known human immunodeficiency virus unless the following requirements are met: 1. CD4 count \>350/µL 2. No AIDS-defining opportunistic infection in the last 12 months 3. Stable anti-retroviral regimen with medications that are not prohibited by the protocol for at least 4 weeks with HIV viral load less than 400 copies/mL prior to enrollment. 18. Known active hepatitis B, active hepatitis C infection or if the participant is taking medications that are prohibited per protocol. 19. If female, the participant is pregnant or lactating. 20. Ongoing participation in an interventional study. 21. For participants receiving inlexisertib and binimetinib combination: Known Gilbert's syndrome

Inclusion Criteria

Exclusion Criteria

1. Male or female participants ≥18 years of age
2. Dose Escalation Phase (Part 1):
1. 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.
2. 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.
3. Participants enrolled in the inlexisertib and sotorasib cohort (Cohort D) must have a KRAS G12C mutation.
3. Dose Expansion Phase (Part 2):
* 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.
4. 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.
5. Must have at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST), v1.1
6. Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 (Dose Escalation) or 0 to 1 (Dose Expansion) at Screening
7. Adequate organ function and bone marrow function.
8. If a female of childbearing potential must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.
9. Male participants must agree to follow contraception requirements.
10. Must provide signed consent to participate in the study and is willing to comply with study-specific procedures.

1. Must not have received the following within the specified time periods prior to the first dose of study drug:
1. 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)
2. 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)
3. 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
4. Grapefruit or grapefruit juice: 14 days
2. 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.
3. Have not recovered from all toxicities from prior therapy according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
4. Presence or history of central nervous system (CNS) metastases or leptomeningeal disease, with some exceptions
5. 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.
6. 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.
7. Left ventricular ejection fraction (LVEF) \<50% at Screening
8. Systemic arterial thrombotic or embolic events within 6 months prior to the first dose of study drug
9. Systemic venous thrombotic events within 1 month prior to the first dose of study drug
10. Malabsorption syndrome
11. 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.
12. Any other clinically significant comorbidities.
13. For participants receiving inlexisertib and trametinib combination or inlexisertib 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.
14. For participants receiving inlexisertib 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.
15. For participants receiving inlexisertib and sotorasib combination: Use of proton pump inhibitors (PPIs) and H2 receptor antagonists that cannot be discontinued 3 days prior to the start of study drug administration.
16. Known allergy or hypersensitivity to any component of the investigational drug products.
17. Known human immunodeficiency virus unless the following requirements are met:
1. CD4 count \>350/µL
2. No AIDS-defining opportunistic infection in the last 12 months
3. Stable anti-retroviral regimen with medications that are not prohibited by the protocol for at least 4 weeks with HIV viral load less than 400 copies/mL prior to enrollment.
18. Known active hepatitis B, active hepatitis C infection or if the participant is taking medications that are prohibited per protocol.
19. If female, the participant is pregnant or lactating.
20. Ongoing participation in an interventional study.
21. For participants receiving inlexisertib and binimetinib combination: Known Gilbert's syndrome

Contacts and Locations

Principal Investigator

Clinical Team

STUDY_DIRECTOR

Deciphera Pharmaceuticals, LLC

Study Locations (Sites)

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Washington University Siteman Cancer Center

St Louis, Missouri, 63108

United States

Rutgers Cancer Institute

New Brunswick, New Jersey, 08901

United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016

United States

Oregon Health and Science University

Portland, Oregon, 97239

United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

NEXT Oncology

Austin, Texas, 78758

United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030

United States

NEXT Oncology

San Antonio, Texas, 78229

United States

University of Wisconsin Clinical Science Center

Madison, Wisconsin, 53792

United States

Collaborators and Investigators

Sponsor: Deciphera Pharmaceuticals, LLC

Clinical Team, STUDY_DIRECTOR, Deciphera Pharmaceuticals, LLC

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-06-15

Study Completion Date2028-08

Study Record Updates

Study Start Date2021-06-15

Study Completion Date2028-08

Terms related to this study

Keywords Provided by Researchers

KRAS G12C

Additional Relevant MeSH Terms

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