A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer

December 18, 2025 updated by: Novartis Pharmaceuticals

A Phase Ib, Multicenter, Open-label Dose Escalation and Expansion Platform Study of Select Drug Combinations in Adult Patients With Advanced or Metastatic BRAF V600 Colorectal Cancer

A phase Ib, open-label platform study of select drug combinations chosen in order to characterize safety and tolerability of each treatment arm tested and to identify recommended doses and regimens for future studies.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a phase Ib, multi-center, open-label study with multiple treatment arms in adult patients with advanced or metastatic BRAF V600 (E, D, or K) in order to characterize safety and tolerability of each treatment arm tested and to identify recommended doses and regimens for future studies. The open platform design of this study is adaptive to allow removal of combination treatment arm(s) based on emerging data and facilitate introduction of new candidate combinations. The study is comprised of a dose escalation part and may be followed by a dose expansion part for any combination treatment arm.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
122

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Novartis Investigative Site
  • Belgium
      • Brussels, Belgium, 1000
        • Novartis Investigative Site
      • Leuven, Belgium, 3000
        • Novartis Investigative Site
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Novartis Investigative Site
  • Germany
      • Dresden, Germany, 01307
        • Novartis Investigative Site
      • Essen, Germany, 45147
        • Novartis Investigative Site
      • Ulm, Germany, 89081
        • Novartis Investigative Site
  • Israel
      • Tel Aviv, Israel, 6423906
        • Novartis Investigative Site
  • Netherlands
      • Zoetermeer, Netherlands, NL-2722 EP
        • Novartis Investigative Site
  • Singapore
      • Singapore, Singapore, 119228
        • Novartis Investigative Site
  • Spain
      • Madrid, Spain, 28009
        • Novartis Investigative Site
    • Catalonia
      • Barcelona, Catalonia, Spain, 08035
        • Novartis Investigative Site
    • Valencia
      • Valencia, Valencia, Spain, 46010
        • Novartis Investigative Site
  • United Kingdom
      • Manchester, United Kingdom, M20 2BX
        • Novartis Investigative Site
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • University of California LA Santa Monica Location
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Massachusetts General Hospital
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute SC
    • Texas
      • Houston, Texas, United States, 77030
        • Uni Of TX MD Anderson Cancer Cntr

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Patients must have a site of disease amenable to biopsy, and be a candidate for tumor biopsy according to the treating institution's guidelines. Patients must be willing to undergo a new tumor biopsy at baseline and during on study therapy. Exceptions may be considered after documented discussion with Novartis.
  • All patients must have a BRAF V600 mutation confirmed by local assessment.
  • Patients with unresectable advanced/metastatic BRAF V600 cancer of the colon or rectum with measurable disease as determined by RECIST v1.1
  • Patients must have documented disease progression following, or are intolerant to, 1 or 2 lines of chemotherapy for advanced/metastatic disease

Key Exclusion Criteria:

  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in-situ cervical cancer, or other tumors that will not affect life expectancy
  • Impairment of gastrointestinal function or gastrointestinal disease that may signficantly alter the absorption of study drugs
  • History of or current evidence/risk of retinal verin occlusion or serous retinopathy
  • History of or current interstitial lung disease or non-infectious pneumonitis
  • Patients with a known history of testing positive for HIV
  • Clinically significant cardiac disease at screening
  • Any medical condition that would, in the investigator's judgment, prevent the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
  • Pregnant or lactating women

Other protocol-defined inclusion/exclusion may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dabrafenib + LTT462 backbone arm 1
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
Drug: Dabrafenib
Capsule for oral use
Other Names:
  • DRB436, Tafinlar
Drug: LTT462
Capsule for oral use
Experimental: Dabrafenib + LTT462 + trametinib triplet arm 1
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
Drug: Dabrafenib
Capsule for oral use
Other Names:
  • DRB436, Tafinlar
Drug: LTT462
Capsule for oral use
Drug: Trametinib
Tablet for oral use
Other Names:
  • TMT212, Mekinist
Experimental: Dabrafenib + LTT462 + LXH254 triplet arm 2
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment.
Drug: Dabrafenib
Capsule for oral use
Other Names:
  • DRB436, Tafinlar
Drug: LTT462
Capsule for oral use
Drug: LXH254
Tablet for oral use
Experimental: Dabrafenib + LTT462 + TNO155 triplet arm 3
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
Drug: Dabrafenib
Capsule for oral use
Other Names:
  • DRB436, Tafinlar
Drug: LTT462
Capsule for oral use
Drug: TNO155
Capsule for oral use
Experimental: Dabrafenib + LTT462 + spartalizumab triplet arm 4
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer - Arm is closed for further enrollment.
Drug: Dabrafenib
Capsule for oral use
Other Names:
  • DRB436, Tafinlar
Drug: LTT462
Capsule for oral use
Biological: Spartalizumab
Liquid in vial (Concentrate for solution for infusion) for intravenous use
Other Names:
  • PDR001
Experimental: Dabrafenib + trametinib + TNO155 triplet arm 5
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
Drug: Dabrafenib
Capsule for oral use
Other Names:
  • DRB436, Tafinlar
Drug: Trametinib
Tablet for oral use
Other Names:
  • TMT212, Mekinist
Drug: TNO155
Capsule for oral use
Experimental: Dabrafenib + LTT462 + Tislelizumab triplet arm 6
dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer
Drug: Dabrafenib
Capsule for oral use
Other Names:
  • DRB436, Tafinlar
Drug: LTT462
Capsule for oral use
Biological: Tislelizumab
Liquid in vial (Concentrate for solution for infusion) for intravenous use
Other Names:
  • VDT482, BGBA317

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence and nature of dose limiting toxicities (DLTs) in the first cycle
Time Frame: 30 months
To characterize safety and tolerability of each treatment arm tested and identify recommended doses (RD) and regimens for future studies
30 months
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, and ECGs
Time Frame: 34 months
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
34 months
Frequency of dose interruptions
Time Frame: 30 months
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
30 months
Frequency of dose reductions
Time Frame: 30 months
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
30 months
Dose intensity
Time Frame: 30 months
To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies
30 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
AUClast derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Time Frame: 30 months
To characterize the PK of each investigational drug within each treatment arm
30 months
Best overall response (BOR)
Time Frame: 34 months
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
34 months
Progression free survival (PFS)
Time Frame: 34 months
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
34 months
Overall response rate (ORR)
Time Frame: 34 months
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
34 months
Duration of response (DOR)
Time Frame: 34 months
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
34 months
Disease control rate (DCR)
Time Frame: 34 months
To evaluate preliminary anti-tumor activity of each treatment arm per RECIST v1.1.
34 months
Change from baseline of the PD marker DUSP6 in tumor tissue (dose escalation only)
Time Frame: 30 months
To evaluate PD effect in their respective combinations in tumor
30 months
AUCtau derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Time Frame: 30 months
To characterize the PK of each investigational drug within each treatment arm
30 months
Cmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Time Frame: 30 months
To characterize the PK of each investigational drug within each treatment arm
30 months
Tmax derived from Serum/plasma concentration of individual investigational drugs within combination treatments
Time Frame: 30 months
To characterize the PK of each investigational drug within each treatment arm
30 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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 Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 22, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 25, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 25, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 2, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 2, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 3, 2020

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 24, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CADPT01C12101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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