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Non-Small Cell Lung CancerPhase 1NCT04892017

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

A Phase 1 study testing Inlexisertib, Trametinib and Binimetinib in people with Non-Small Cell Lung Cancer and Advanced Solid Tumor, run by Deciphera Pharmaceuticals, LLC at 10 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Inlexisertib, Trametinib and Binimetinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
91 participants
Where
10 sitesUnited States
Study dates
15 Jun 2021to 30 Mar 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • Eastern Cooperative Oncology Group (ECOG) score of 0 to 2 (Dose Escalation) or 0 to 1 (Dose Expansion) at Screening
  • Adequate organ function and bone marrow function.
  • If a female of childbearing potential must have a negative pregnancy test prior to enrollment and agree to follow the contraception requirements.
  • Male participants must agree to follow contraception requirements.
  • Must provide signed consent to participate in the study and is willing to comply with study-specific procedures.

Who cannot join

  • 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.
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  • 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.
  • Any other clinically significant comorbidities.
  • 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.
  • 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.
  • 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.
  • Known allergy or hypersensitivity to any component of the investigational drug products.
  • Known human immunodeficiency virus unless the following requirements are met:
  • CD4 count >350/µL
  • No AIDS-defining opportunistic infection in the last 12 months
  • 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.
  • Known active hepatitis B, active hepatitis C infection or if the participant is taking medications that are prohibited per protocol.
  • If female, the participant is pregnant or lactating.
  • Ongoing participation in an interventional study.
  • For participants receiving inlexisertib and binimetinib combination: Known Gilbert's syndrome

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • NEXT Oncology

    Austin, Texas, 78758

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Wisconsin Clinical Science Center

    Madison, Wisconsin, 53792

  • Rutgers Cancer Institute

    New Brunswick, New Jersey, 08901

  • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

    New York, New York, 10016

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • NEXT Oncology

    San Antonio, Texas, 78229

  • Washington University Siteman Cancer Center

    St Louis, Missouri, 63108

Other trials in United States

About this study

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

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.

Being tested
Inlexisertib, Trametinib, Binimetinib, Sotorasib
Keywords
KRAS G12C
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • InlexisertibDrug

    Also called DCC-3116

    Oral Tablet Formulation

  • TrametinibDrug

    Oral Tablet Formulation

  • BinimetinibDrug

    Oral Tablet Formulation

  • SotorasibDrug

    Oral Tablet Formulation

Study groups in NCT04892017
Study groupRoleWhat they receive
Dose Escalation (Part 1, Cohort A Monotherapy)ExperimentalInlexisertib 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.
Receives: Drug: Inlexisertib
Dose Escalation (Part 1, Cohort B Combination)ExperimentalUpon determination of the RP2D/MTD single agent, inlexisertib will be dosed in combination with trametinib. Escalation Cohort B combination closed on January 8, 2024.
Receives: Drug: Inlexisertib; Drug: Trametinib
Dose Escalation (Part 1, Cohort C Combination)ExperimentalUpon determination of the RP2D/MTD single agent, inlexisertib will be dosed in combination with binimetinib. Escalation Cohort C combination closed on January 8, 2024.
Receives: Drug: Inlexisertib; Drug: Binimetinib
Dose Escalation (Part 1, Cohort D Combination)ExperimentalUpon determination of the RP2D/MTD single agent, inlexisertib will be dosed in combination with sotorasib.
Receives: Drug: Inlexisertib; Drug: Sotorasib
Expansion Cohorts 1, 2, 3 and 4 (Part 2)ExperimentalExpansion Cohorts 1, 2, 3 and 4 inlexisertib combinations will not open for enrollment.
Receives: Drug: Inlexisertib
Expansion Cohort 5 (Part 2)ExperimentalInlexisertib 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.
Receives: Drug: Inlexisertib; Drug: Sotorasib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Approximately 24 months

  2. 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.

    Measured: Approximately 18 months

  3. Objective response rate (ORR) (Expansion Phase)

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

    Measured: Approximately 24 months

Secondary outcomes (8)

  1. Duration of response (DoR)

    DoR is defined as the time interval from the time that the measurement criteria are first met for CR or PR (whichever is first recorded) until the first date that the progressive disease is objectively documented or death, whichever occurs first.

    Measured: Approximately 24 months

  2. Disease Control Rate (DCR)

    The DCR is defined as the proportion of participants who achieve CR, PR, or stable disease (SD) at the specified time point per RECIST v1.1.

    Measured: Approximately 24 months

  3. Time to response

    Time to response is defined as the time from initiation of treatment until the first assessment demonstrating CR or PR per RECIST v1.1.

    Measured: Approximately 24 months

  4. Progression-free survival (PFS)

    PFS is defined as the time from initiation of treatment until documented disease progression per RECIST v1.1 or death, whichever occurs first.

    Measured: Approximately 24 months

  5. Maximum observed concentration (Cmax)

    Measure the maximum observed concentration of inlexisertib (single-agent and combinations).

    Measured: Predose and up to 12 hours postdose

  6. Time to maximum observed concentration (Tmax)

    Measure the time to maximum plasma concentration of inlexisertib (single-agent and combinations).

    Measured: Predose and up to 12 hours postdose

  7. Minimum observed concentration (Cmin)

    Measure the minimum observed concentration of inlexisertib (single-agent and combinations).

    Measured: Predose and up to 12 hours postdose

  8. Area under the concentration-time curve (AUC)

    Measure the AUC of inlexisertib (single-agent and combinations).

    Measured: Predose and up to 12 hours postdose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 May 2021
  2. Study start15 Jun 2021
  3. Primary completion30 Mar 2026
  4. Study completion30 Mar 2026

Why it stopped: Trial terminated due to business decision, not based on any safety or efficacy concerns.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
91 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04892017
Sponsor's protocol ID
DCC-3116-01-001
Other IDs
2022-501474-19-00
Status last verified
Apr 2026
First submitted
6 May 2021
Last updated
8 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Inlexisertib, Trametinib and Binimetinib in people with Non-Small Cell Lung Cancer and Advanced Solid Tumor, run by Deciphera Pharmaceuticals, LLC at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Trial terminated due to business decision, not based on any safety or efficacy concerns.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Adverse Events (time frame: Approximately 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04892017.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2026.

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