Clinical trial NCT06194877: A Study to Investigate BGB-3245 (Brimarafenib) With Panitumumab in Participants With Advanced or Metastatic RAS Mutant Colorectal and Pancreatic Ductal Cancers
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Colorectal Cancer
Pancreatic Ductal Cancer
Advanced or Metastatic RAS Mutant Colorectal and Pancreatic Ductal Cancers
Keywords: Advanced or Metastatic RAS mutant Colorectal and Pancreatic Ductal Cancers
BGB-3245
Panitumumab
Brimarafenib
BRAF
KRAS
NRAS
Lead sponsor: MapKure, LLC
Sponsor class: INDUSTRY
First posted: 2024-01-08
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to approximately 2 years
measure: Part 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately 2 years
measure: Part 1: Number of Participants with Adverse Events of Special Interest (AESIs)
timeFrame: Up to approximately 2 years
measure: Part 1: Number of Participants with Interruptions to Dosing with BGB-3245
timeFrame: Up to approximately 2 years
measure: Part 1: Number of Participants with Reductions in Dosing with BGB-3245
timeFrame: Up to approximately 2 years
measure: Part 1: MTD of BGB-3245
timeFrame: Up to approximately 2 years
measure: Part 1: RP2D of BGB-3245
timeFrame: Up to approximately 2 years
measure: Part 2: ORR as Assessed by Initial Investigator Review
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Part 1 and 2: Plasma Concentrations of BGB-3245 and Any Relevant Metabolites
timeFrame: Day 1 of each 28 day cycle (up to approximately 2 years)
measure: Part 1: ORR as Assessed by Investigator Review using RECIST v1.1
timeFrame: Up to approximately 2 years
measure: Part 2: ORR as Assessed by Central Review
timeFrame: Up to approximately 2 years
measure: Part 1 and 2: Duration of Response (DoR)
timeFrame: Up to approximately 2 years
measure: Part 1 and 2: Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Part 1 and 2: Progression Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Part 2: Number of Participants with SAEs
timeFrame: Up to approximately 2 years
measure: Part 2: Number of Participants with TEAEs
timeFrame: Up to approximately 2 years
measure: Part 2: Number of Participants with AESIs
timeFrame: Up to approximately 2 years
measure: Part 2: Number of Participants with Interruptions to Dosing with BGB-3245
timeFrame: Up to approximately 2 years
measure: Part 2: Number of Participants with Reductions in Dosing with BGB-3245
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center - Duarte
state: California
city: Durham
country: United States
facility: Duke Cancer Institute
state: North Carolina
city: Fairfax
country: United States
facility: USOR - Virginia Cancer Specialists - Fairfax Office
state: Virginia
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
Study officials:
References: