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

NCT04294160 | Terminated Phase 1 FDA Drug

• 1 other identifier: CADPT01C12101
• Study Type: interventional
• Target: 122
• Locations: 10 countries
• Sites: 18

Brief Summary

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.

Conditions

BRAF V600 Colorectal Cancer

Keywords

Phase Ib, BRAF-mutated, BRAF V600E, BRAF V600D, BRAF V600K, colorectal cancer, colon cancer, rectal cancer, metastatic, BLRM with EWOC

Outcome Measures

Primary Outcomes (5)

• Incidence and nature of dose limiting toxicities (DLTs) in the first cycle

  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

  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

  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

  To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies

  30 months

• Dose intensity

  To characterize safety and tolerability of each treatment arm tested and identify recommended doses and regimens for future studies

  30 months

Secondary Outcomes (10)

• AUClast derived from Serum/plasma concentration of individual investigational drugs within combination treatments

  30 months

• Best overall response (BOR)

  34 months

• Progression free survival (PFS)

  34 months

• Overall response rate (ORR)

  34 months

• Duration of response (DOR)

  34 months

Study Arms (7)

Dabrafenib + LTT462 backbone arm 1

EXPERIMENTAL

dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer

Drug: Dabrafenib; Drug: LTT462

Dabrafenib + LTT462 + trametinib triplet arm 1

EXPERIMENTAL

dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer

Drug: Dabrafenib; Drug: LTT462; Drug: Trametinib

Dabrafenib + LTT462 + LXH254 triplet arm 2

EXPERIMENTAL

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; Drug: LTT462; Drug: LXH254

Dabrafenib + LTT462 + TNO155 triplet arm 3

EXPERIMENTAL

dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer

Drug: Dabrafenib; Drug: LTT462; Drug: TNO155

Dabrafenib + LTT462 + spartalizumab triplet arm 4

EXPERIMENTAL

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; Drug: LTT462; Biological: Spartalizumab

Dabrafenib + trametinib + TNO155 triplet arm 5

EXPERIMENTAL

dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer

Drug: Dabrafenib; Drug: Trametinib; Drug: TNO155

Dabrafenib + LTT462 + Tislelizumab triplet arm 6

EXPERIMENTAL

dose escalation to determine maximum tolerated dose (MTD)/ Recommended dose (RD) in adult patients with advanced or metastatic BRAF V600 colorectal cancer

Drug: Dabrafenib; Drug: LTT462; Biological: Tislelizumab

Interventions

Dabrafenib DRUG

Capsule for oral use

Also known as: DRB436, Tafinlar

Dabrafenib + LTT462 + LXH254 triplet arm 2; Dabrafenib + LTT462 + TNO155 triplet arm 3; Dabrafenib + LTT462 + Tislelizumab triplet arm 6; Dabrafenib + LTT462 + spartalizumab triplet arm 4; Dabrafenib + LTT462 + trametinib triplet arm 1; Dabrafenib + LTT462 backbone arm 1; Dabrafenib + trametinib + TNO155 triplet arm 5

LTT462 DRUG

Capsule for oral use

Dabrafenib + LTT462 + LXH254 triplet arm 2; Dabrafenib + LTT462 + TNO155 triplet arm 3; Dabrafenib + LTT462 + Tislelizumab triplet arm 6; Dabrafenib + LTT462 + spartalizumab triplet arm 4; Dabrafenib + LTT462 + trametinib triplet arm 1; Dabrafenib + LTT462 backbone arm 1

Trametinib DRUG

Tablet for oral use

Also known as: TMT212, Mekinist

Dabrafenib + LTT462 + trametinib triplet arm 1; Dabrafenib + trametinib + TNO155 triplet arm 5

LXH254 DRUG

Tablet for oral use

Dabrafenib + LTT462 + LXH254 triplet arm 2

TNO155 DRUG

Capsule for oral use

Dabrafenib + LTT462 + TNO155 triplet arm 3; Dabrafenib + trametinib + TNO155 triplet arm 5

Spartalizumab BIOLOGICAL

Liquid in vial (Concentrate for solution for infusion) for intravenous use

Also known as: PDR001

Dabrafenib + LTT462 + spartalizumab triplet arm 4

Tislelizumab BIOLOGICAL

Liquid in vial (Concentrate for solution for infusion) for intravenous use

Also known as: VDT482, BGBA317

Dabrafenib + LTT462 + Tislelizumab triplet arm 6

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (18)

University of California LA Santa Monica Location

Los Angeles, California, 90095, United States

Location

Massachusetts General Hospital Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Sarah Cannon Research Institute SC

Nashville, Tennessee, 37203, United States

Location

Uni Of TX MD Anderson Cancer Cntr

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

Westmead, New South Wales, 2145, Australia

Location

Novartis Investigative Site

Brussels, 1000, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Ulm, 89081, Germany

Location

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Zoetermeer, NL-2722 EP, Netherlands

Location

Novartis Investigative Site

Singapore, 119228, Singapore

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Manchester, M20 2BX, United Kingdom

Location

Related Links

• CADPT01C12101 Clinical Trial results Form
• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms; Neoplasm Metastasis

Interventions

dabrafenib; trametinib; naporafenib; spartalizumab; tislelizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 2, 2020
• First Posted: March 3, 2020
• Study Start: July 22, 2020
• Primary Completion: September 25, 2024
• Study Completion: September 25, 2024
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); ES (3); CA (1); GB (1); NL (1); SG (1); BE (2); AU (1); DE (3); IL (1)