A Study to Investigate BGB-3245 (Brimarafenib) With Panitumumab in Participants With Advanced or Metastatic RAS Mutant Colorectal and Pancreatic Ductal Cancers

NCT ID: NCT06194877

Last Updated: 2025-04-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-18
• Study Completion Date: 2025-03-10

Brief Summary

The primary objectives of Part 1 of this study are to:

• Assess the safety and tolerability of the combination of BGB-3245 and panitumumab in participants with advanced or metastatic colorectal cancer (CRC) with a known mutation status and tumor harboring an oncogenic mutation of v-Raf murine sarcoma viral oncogene homolog B; B-RAF proto-oncogene, serine/threonine kinase (BRAF), Kirsten rat sarcoma viral oncogene homolog (KRAS), or neuroblastoma RAS viral oncogene homolog (NRAS) with documented disease progression during or after at least 1 line of prior therapy.
• Determine the maximum tolerated dose (MTD) of BGB-3245 in combination with panitumumab and the recommended phase 2 dose (RP2D) of the combination.

The primary objective of Part 2 of this study is to determine the objective response rate (ORR) as assessed by initial investigator review using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 with BGB-3245 and panitumumab combination treatment at the RP2D.

Conditions

Colorectal Cancer; Pancreatic Ductal Cancer; Advanced or Metastatic RAS Mutant Colorectal and Pancreatic Ductal Cancers

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Dose Finding Part

Participants with advanced or metastatic CRC and with known mutation status and tumor harboring an oncogenic mutation of BRAF, KRAS, or NRAS and with documented disease progression by RECIST during or after at least 1 line of prior therapy will be enrolled into 4 planned sequentially run cohorts. Participants will receive escalating doses of BGB-3245 in combination with panitumumab to establish the MTD and RP2D by assessing the safety, tolerability, preliminary antitumor activity, and pharmacokinetics (PK) for the combination of BGB-3245 with panitumumab.

Group Type: EXPERIMENTAL

BGB-3245

Intervention Type: DRUG

Oral capsule

Panitumumab

Intervention Type: DRUG

Intravenous (IV) infusion via an infusion pump

Part 2: Dose Expansion Part, Group 1

Participants with advanced or metastatic CRC that harbors KRAS or NRAS mutations who have been treated and had documented disease progression by RECIST criteria during or after at least 1 line of prior therapy. Participants will receive the RP2D of BGB-3245 in combination with panitumumab to further evaluate the safety, PK, and assess the preliminary antitumor activity of the RP2D of the BGB-3245 and panitumumab combination.

Group Type: EXPERIMENTAL

BGB-3245

Intervention Type: DRUG

Oral capsule

Panitumumab

Intervention Type: DRUG

Intravenous (IV) infusion via an infusion pump

Part 2: Dose Expansion Part, Group 2

Participants with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) that harbors KRAS mutations who have been treated and had documented disease progression by RECIST criteria during or after at least 1 line of prior therapy. Participants will receive the RP2D of BGB-3245 in combination with panitumumab to further evaluate the safety, PK, and assess the preliminary antitumor activity of the RP2D of the BGB-3245 and panitumumab combination.

Group Type: EXPERIMENTAL

BGB-3245

Intervention Type: DRUG

Oral capsule

Panitumumab

Intervention Type: DRUG

Intravenous (IV) infusion via an infusion pump

Interventions

BGB-3245

Oral capsule

Intervention Type: DRUG

Panitumumab

Intravenous (IV) infusion via an infusion pump

Intervention Type: DRUG

Other Intervention Names

Brimarafenib; Vectibix®

Eligibility Criteria

Inclusion Criteria

1. Participants with histologically confirmed advanced or metastatic solid tumors who have had documented disease progression by RECIST criteria during or after at least 1 prior line of systemic anticancer therapies in the representative population or are unable to receive standard of care therapy(ies) as noted by local guidelines.

2. Part 1 (Dose Finding): Participants with CRC with a known mutation status by local testing and tumor harboring an oncogenic mutation of BRAF, KRAS, or NRAS in the archival tumor sample or fresh tumor biopsy.

3. Part 2 (Dose Expansion): Participants must have a known mutation status by local testing and meet one of the following criteria according to the group they are enrolled into: Group 1: Participants with CRC that harbors KRAS or NRAS mutations in the archival tumor sample or fresh tumor biopsy. Group 2: Participants with PDAC that harbors KRAS mutations in the archival tumor sample or fresh tumor biopsy.

4. Participants must provide archival tumor tissue or a fresh tumor biopsy for retrospective mutation status analysis.

5. Participants must have radiologically measurable disease as defined per RECIST v1.1 at screening.

6. Eastern Cooperative Oncology Group performance status of ≤1 at screening.

7. Adequate hematologic and organ function, as indicated by defined laboratory values, prior to Cycle 1 Day 1.

8. Adequate cardiac function.

Exclusion Criteria

1. Participants receiving cancer therapy (chemotherapy or other systemic anticancer therapies, immunotherapy, radiation therapy, or surgery) at the time of Cycle 1 Day 1.

2. Active infection requiring systemic treatment at the start of the study treatment.

3. Clinically significant cardiovascular disease and / or events within 6 months of signing the informed consent form.

4. Participants with toxicities that have not recovered to Grade ≤1 or stabilized and those Grade 2 toxicities listed as permitted in other eligibility criteria.

5. Participants with a history of pneumonitis or interstitial lung disease.

6. Participants with immune-related toxicities that have not resolved with appropriate management.

7. History or presence of gastrointestinal disease or other condition known to interfere with the absorption of drugs.

8. History of ulcerative colitis or Crohn's disease or protracted and ongoing immune-mediated diarrhea from prior checkpoint inhibitor use.

9. History of corneal perforation, keratitis, or severe dry eye.

10. Current evidence of symptomatic central nervous system metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression.

11. Any active malignancy ≤3 years before Cycle 1 Day 1 except for the specific cancer under investigation in this study and any localized or noninvasive cancer that has been treated curatively.

12. Known hypersensitivity to rapidly accelerated fibrosarcoma (RAF) inhibitors, anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, or their excipients.

13. Any known history of Grade ≥3 toxicity lasting >14 days from another RAF, mitogen activated protein kinase, extracellular signal-regulated kinase, or anti-EGFR antibody inhibitor requiring discontinuation of treatment from these drugs.

14. Receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer ≤14 days (or 5 half-lives, whichever is longer) before Cycle 1 Day 1 and until completion of dosing with BGB-3245 for at least 5 half-lives.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MapKure, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

City of Hope Comprehensive Cancer Center - Duarte

Duarte, California, United States

Duke Cancer Institute

Durham, North Carolina, United States

USOR - Virginia Cancer Specialists - Fairfax Office

Fairfax, Virginia, United States

Westmead Hospital

Westmead, New South Wales, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Countries

United States; Australia

Other Identifiers

BGB-3245-EGFR-001

Identifier Type: -

Identifier Source: org_study_id