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

Colorectal Cancer Clinical Trial

Official title:

A Phase 1b, Open-Label, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 With Panitumumab in Patients With Advanced or Metastatic RAS Mutant Colorectal and Pancreatic Ductal Cancers

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06194877
• Other study ID #: BGB-3245-EGFR-001
• Status: Recruiting
• Phase: Phase 1
• Start date: April 18, 2024
• Est. completion date: May 24, 2027

Study information

• Verified date: May 2024
• Source: MapKure, LLC
• Contact: MapKure
• Phone: 1-877-828-5568
• Email: clinicaltrials[@]mapkure.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: May 24, 2027
• Est. primary completion date: May 24, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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.

Key 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply. Summary of key criteria provided.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Pancreatic Ductal Cancer

Intervention

Drug:
• BGB-3245
Oral capsule
• Panitumumab
Intravenous (IV) infusion via an infusion pump

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Westmead Hospital	Westmead	New South Wales
United States	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

Sponsors (1)

Lead Sponsor	Collaborator
MapKure, LLC

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of Participants with Serious Adverse Events (SAEs)		Up to approximately 2 years
Primary	Part 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs)		Up to approximately 2 years
Primary	Part 1: Number of Participants with Adverse Events of Special Interest (AESIs)		Up to approximately 2 years
Primary	Part 1: Number of Participants with Interruptions to Dosing with BGB-3245		Up to approximately 2 years
Primary	Part 1: Number of Participants with Reductions in Dosing with BGB-3245		Up to approximately 2 years
Primary	Part 1: MTD of BGB-3245		Up to approximately 2 years
Primary	Part 1: RP2D of BGB-3245		Up to approximately 2 years
Primary	Part 2: ORR as Assessed by Initial Investigator Review		Up to approximately 2 years
Secondary	Part 1 and 2: Plasma Concentrations of BGB-3245 and Any Relevant Metabolites		Day 1 of each 28 day cycle (up to approximately 2 years)
Secondary	Part 1: ORR as Assessed by Investigator Review using RECIST v1.1		Up to approximately 2 years
Secondary	Part 2: ORR as Assessed by Central Review		Up to approximately 2 years
Secondary	Part 1 and 2: Duration of Response (DoR)		Up to approximately 2 years
Secondary	Part 1 and 2: Disease Control Rate (DCR)		Up to approximately 2 years
Secondary	Part 1 and 2: Progression Free Survival (PFS)		Up to approximately 2 years
Secondary	Part 2: Number of Participants with SAEs		Up to approximately 2 years
Secondary	Part 2: Number of Participants with TEAEs		Up to approximately 2 years
Secondary	Part 2: Number of Participants with AESIs		Up to approximately 2 years
Secondary	Part 2: Number of Participants with Interruptions to Dosing with BGB-3245		Up to approximately 2 years
Secondary	Part 2: Number of Participants with Reductions in Dosing with BGB-3245		Up to approximately 2 years