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
Overview
- Phase
- Phase 1
- Intervention
- BGB-3245
- Conditions
- Colorectal Cancer
- Sponsor
- MapKure, LLC
- Enrollment
- 13
- Locations
- 5
- Primary Endpoint
- Part 1: MTD of BGB-3245
- Status
- Terminated
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •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.
- •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.
- •Participants must provide archival tumor tissue or a fresh tumor biopsy for retrospective mutation status analysis.
- •Participants must have radiologically measurable disease as defined per RECIST v1.1 at screening.
- •Eastern Cooperative Oncology Group performance status of ≤1 at screening.
- •Adequate hematologic and organ function, as indicated by defined laboratory values, prior to Cycle 1 Day
- •Adequate cardiac function.
Exclusion Criteria
- •Participants receiving cancer therapy (chemotherapy or other systemic anticancer therapies, immunotherapy, radiation therapy, or surgery) at the time of Cycle 1 Day
- •Active infection requiring systemic treatment at the start of the study treatment.
- •Clinically significant cardiovascular disease and / or events within 6 months of signing the informed consent form.
- •Participants with toxicities that have not recovered to Grade ≤1 or stabilized and those Grade 2 toxicities listed as permitted in other eligibility criteria.
- •Participants with a history of pneumonitis or interstitial lung disease.
- •Participants with immune-related toxicities that have not resolved with appropriate management.
- •History or presence of gastrointestinal disease or other condition known to interfere with the absorption of drugs.
- •History of ulcerative colitis or Crohn's disease or protracted and ongoing immune-mediated diarrhea from prior checkpoint inhibitor use.
- •History of corneal perforation, keratitis, or severe dry eye.
- •Current evidence of symptomatic central nervous system metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression.
Arms & Interventions
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.
Intervention: BGB-3245
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.
Intervention: Panitumumab
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.
Intervention: BGB-3245
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.
Intervention: Panitumumab
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.
Intervention: BGB-3245
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.
Intervention: Panitumumab
Outcomes
Primary Outcomes
Part 1: MTD of BGB-3245
Time Frame: Up to approximately 2 years
Part 1: RP2D of BGB-3245
Time Frame: Up to approximately 2 years
Part 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Time Frame: Up to approximately 2 years
Part 2: ORR as Assessed by Initial Investigator Review
Time Frame: Up to approximately 2 years
Part 1: Number of Participants with Serious Adverse Events (SAEs)
Time Frame: Up to approximately 2 years
Part 1: Number of Participants with Reductions in Dosing with BGB-3245
Time Frame: Up to approximately 2 years
Part 1: Number of Participants with Adverse Events of Special Interest (AESIs)
Time Frame: Up to approximately 2 years
Part 1: Number of Participants with Interruptions to Dosing with BGB-3245
Time Frame: Up to approximately 2 years
Secondary Outcomes
- Part 2: ORR as Assessed by Central Review(Up to approximately 2 years)
- Part 1 and 2: Duration of Response (DoR)(Up to approximately 2 years)
- Part 2: Number of Participants with SAEs(Up to approximately 2 years)
- Part 2: Number of Participants with TEAEs(Up to approximately 2 years)
- 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))
- Part 1: ORR as Assessed by Investigator Review using RECIST v1.1(Up to approximately 2 years)
- Part 1 and 2: Disease Control Rate (DCR)(Up to approximately 2 years)
- Part 1 and 2: Progression Free Survival (PFS)(Up to approximately 2 years)
- Part 2: Number of Participants with AESIs(Up to approximately 2 years)
- Part 2: Number of Participants with Interruptions to Dosing with BGB-3245(Up to approximately 2 years)
- Part 2: Number of Participants with Reductions in Dosing with BGB-3245(Up to approximately 2 years)