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

MapKure

Status and phase: Enrolling; Phase 1

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

Treatments: Drug: Panitumumab; Drug: BGB-3245

Study type: Interventional

Funder types: Industry

Identifiers

NCT06194877

BGB-3245-EGFR-001

Details and patient eligibility

About

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.

Enrollment: 64 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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64 participants in 3 patient groups

Part 1: Dose Finding Part

Experimental group

Description:

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.

Treatment:

Drug: BGB-3245

Drug: Panitumumab

Part 2: Dose Expansion Part, Group 1

Experimental group

Description:

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.

Treatment:

Drug: BGB-3245

Drug: Panitumumab

Part 2: Dose Expansion Part, Group 2

Experimental group

Description:

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.

Treatment:

Drug: BGB-3245

Drug: Panitumumab