Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors

Sponsor

MapKure, LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04249843

Collaborator

(none)

168

Enrollment

Locations

Arms

39.4

Anticipated Duration (Months)

33.6

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and antitumor activity of BGB-3245 in participants with advanced or refractory solid tumors

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor B-Raf Mutation-Related Tumors	Drug: BGB-3245	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

168 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A First-in-Human, Phase 1a/1b, Open Label, Dose-Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, and Antitumor Activity of the RAF Dimer Inhibitor BGB-3245 in Patients With Advanced or Refractory Tumors

Actual Study Start Date :

Feb 17, 2020

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1a: Dose Escalation BGB-3245 administered orally (PO)	Drug: BGB-3245 administered orally (PO)
Experimental: Phase 1b, Group 1: Dose Expansion BGB-3245 administered orally (PO)	Drug: BGB-3245 administered orally (PO)

Arm

Intervention/Treatment

Experimental: Phase 1a: Dose Escalation

BGB-3245 administered orally (PO)

Drug: BGB-3245

administered orally (PO)

Experimental: Phase 1b, Group 1: Dose Expansion

BGB-3245 administered orally (PO)

Drug: BGB-3245

administered orally (PO)

Outcome Measures

Primary Outcome Measures

Phase 1a: Number of Participants and Severity Experiencing Adverse Events (AEs) [Up to 30 days after the last dose of study drug]
Phase 1a: Number of Participants and Severity Experiencing Serious Adverse Events (SAEs) [Up to 30 days after the last dose of study drug]
Phase 1a: number of Participants Experiencing AEs meeting protocol defined Dose-Limiting Toxicity (DLT) criteria [From Cycle 1 Day to the end of Cycle 1 (Cycle 1 is 30 days)]
Phase 1a: Maximum Tolerated Dose (MTD) of BGB-3245, and the recommended Phase 2 Dose (RP2D) for BGB-3245 [From Cycle 1 Day to the end of Cycle 1 (Cycle 1 is 30 days)]
The MTD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 33%.
Phase 1b: Objective Response Rate (ORR) confirmed Complete Response and Partial Response [Up to 24 months]

Secondary Outcome Measures

Phase 1a: Overall Response Rate (ORR) as Assessed by the Investigator [Up to 24 months]
Phase 1a: Duration of Response (DOR) as Assessed by the Investigator [Up to 24 months]
Phase 1a: Clinical Benefit Rate (CBR) as Assessed by the Investigator [Up to 24 months]
Phase 1a: Best Overall Response (BOR) as Assessed by the Investigator [Up to 24 months]
Phase 1a: Duration of Stable Disease (DSD) [Up to 24 months]
Phase 1a: Progression Free Survival (PFS) [Up to 24 months]
Phase 1a: Plasma Concentration of BGB-3245 [Within 60 minutes predose up to 72 hours postdose]
Phase 1a: Maximum Observed Plasma Concentration (Cmax) of BGB-3245 [Within 60 minutes predose up to 72 hours postdose]
Phase 1a: Time to Maximum Plasma Concentration (Tmax) of BGB-3245 [60 minutes predose up to 72 hours postdose]
Phase 1a: Time Taken for Half the Initial Dose Administered To Be Eliminated From The Body (T1/2) of BGB-3245 [60 minutes predose up to 72 hours postdose]
Phase 1a: Area Under the Concentration-Time Curve of 0-infinity Days (AUC0-inf) of BGB-3245 [60 minutes predose up to 72 hours postdose]
Phase 1a:Area Under the Concentration-Time Curve of 0-Last hour (AUC0-last) of BGB-3245 [60 minutes predose up to 72 hours postdose]
Phase 1a: Drug Clearance (CL/F) of BGB-3245 [60 minutes predose up to 72 hours postdose]
Phase 1a: Apparent Volume of Distribution (Vz/F) of BGB-3245 [60 minutes predose up to 72 hours postdose]
Phase 1a: Steady State Area Under the Concentration-Time Curve of 0- Last hour (AUCLast, ss) of BGB-3245 [60 minutes predose up to 72 hours postdose]
Phase 1a: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-3245 [60 minutes predose up to 72 hours postdose]
Phase 1a: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-3245 [60 minutes predose up to 72 hours postdose]
Phase 1b: Progression-free survival (PFS) as Assessed by the Investigator [Up to 36 months]
Phase 1b: Duration of Response (DOR) as Assessed by the Investigator [Up to 24 months]
Phase 1b: Disease-Control Rate (DCR) as Assessed by the Investigator [Up to 24 months]
Phase 1b: Duration of Stable Disease (DSD) as Assessed by the Investigator [Up to 24 months]
Phase 1b: Clinical Benefit Rate (CBR) as Assessed by the Investigator [Up to 24 months]
Phase 1b: Overall Survival [Up to 36 months]
Phase 1b: Number of Participants Experiencing Adverse Events (AEs) [Up to 30 days after the last dose of study drug]
Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs) [Up to 30 days after the last dose of study drug]
Phase 1b: Plasma Concentration of BGB-3245 [60 minutes predose up to 3 hours postdose]
Phase 1b: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-3245 [60 minutes predose up to 72 hours postdose]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Participants with histologically confirmed advanced or metastatic solid tumor who have experienced disease progression during or after at least 1 line of prior systemic anticancer therapy, or for whom treatment is not available or not tolerated/acceptable to the participants. In addition, participants must meet the following eligibility criteria for the corresponding phase of the study:
Phase 1a: participants with a known mutation status and tumor harboring an oncogenic mutation of the v-RAF murine sarcoma viral oncogene homolog B (BRAF) gene (the mutations of primary interest are the BRAF Class II mutation, Class III mutation or BRAF fusion). In addition, participants with melanoma harboring the mutation of the neuroblastoma RAS viral oncogene homolog (NRAS) gene are eligible for Part 1a.
Phase 1b: participants must have a known mutation status and meet one of the following criteria according to the group they are enrolled into:

Group 1: participants with solid tumors harboring a BRAF Class II mutation

Group 2: participants with solid tumors harboring a BRAF Class III mutation
Group 3: participants with solid tumors harboring a BRAF fusion mutation
Group 4: participants with cutaneous melanoma harboring a NRAS mutation
Group 5: participants with cutaneous melanoma harboring a NRAS mutation that consent to paired fresh biopsies inhibitor resistant tumors.

Participants must provide archival tumor tissue or agree to a fresh tumor biopsy for mutation and biomarkers analysis (fresh tumor biopsies are strongly recommended at Screening in participants with readily accessible tumor lesions who are not receiving anticoagulants).3. Patients must have radiologically measurable disease as defined per RECIST v1.1.

Key Exclusion Criteria:

Participants receiving cancer therapy (chemotherapy or other systemic anticancer therapies, immunotherapy, radiation therapy, or surgery) at the time of Cycle 1 Day 1.
All participants who have received prior systemic anticancer treatment within the following time frames will be excluded:
Cyclical chemotherapy within a period of time that is shorter than the cycle length used for that treatment (i.e., 6 weeks for nitrosourea, mitomycin C) prior to Cycle 1 Day 1; and
Biologic therapy (i.e., antibodies), continuous or intermittent small-molecule therapies, or any other investigational agents within a period of 5 times the half-life of the agent or ≤4 weeks (whichever is shorter) prior to Cycle 1 Day 1.
History or presence of gastrointestinal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
Current evidence of symptomatic CNS metastases, leptomeningeal carcinomatosis or untreated spinal cord compression. Asymptomatic treated or asymptomatic untreated brain metastases are allowed as long as patients are clinically stable.
Any unstable, preexisting major medical condition that in the opinion of the investigator contraindicates the use of a study drug, including known human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
3	MD Anderson	Houston	Texas	United States	77030
4	Peter MacCallum Cancer Centre	Melbourne		Australia	2010
5	The Kinghorn Cancer Centre, St Vincent Hospital Sydney	Sydney		Australia	2010