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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06194877

Registration number

NCT06194877

Ethics application status

Date submitted

22/12/2023

Date registered

8/01/2024

Date last updated

6/06/2024

Titles & IDs

Public title

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

Scientific 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

Secondary ID [1]

BGB-3245-EGFR-001

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Colorectal Cancer

Pancreatic Ductal Cancer

Advanced or Metastatic RAS Mutant Colorectal and Pancreatic Ductal Cancers

Condition category

Condition code

Cancer

Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Treatment: Drugs - BGB-3245
Treatment: Drugs - Panitumumab

Experimental: 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.

Experimental: 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.

Experimental: 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.

Treatment: Drugs: BGB-3245
Oral capsule

Treatment: Drugs: Panitumumab
Intravenous (IV) infusion via an infusion pump

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Part 1: Number of Participants with Serious Adverse Events (SAEs)

Timepoint [1]

Up to approximately 2 years

Primary outcome [2]

Part 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs)

Timepoint [2]

Up to approximately 2 years

Primary outcome [3]

Part 1: Number of Participants with Adverse Events of Special Interest (AESIs)

Timepoint [3]

Up to approximately 2 years

Primary outcome [4]

Part 1: Number of Participants with Interruptions to Dosing with BGB-3245

Timepoint [4]

Up to approximately 2 years

Primary outcome [5]

Part 1: Number of Participants with Reductions in Dosing with BGB-3245

Timepoint [5]

Up to approximately 2 years

Primary outcome [6]

Part 1: MTD of BGB-3245

Timepoint [6]

Up to approximately 2 years

Primary outcome [7]

Part 1: RP2D of BGB-3245

Timepoint [7]

Up to approximately 2 years

Primary outcome [8]

Part 2: ORR as Assessed by Initial Investigator Review

Timepoint [8]

Up to approximately 2 years

Secondary outcome [1]

Part 1 and 2: Plasma Concentrations of BGB-3245 and Any Relevant Metabolites

Timepoint [1]

Day 1 of each 28 day cycle (up to approximately 2 years)

Secondary outcome [2]

Part 1: ORR as Assessed by Investigator Review using RECIST v1.1

Timepoint [2]

Up to approximately 2 years

Secondary outcome [3]

Part 2: ORR as Assessed by Central Review

Timepoint [3]

Up to approximately 2 years

Secondary outcome [4]

Part 1 and 2: Duration of Response (DoR)

Timepoint [4]

Up to approximately 2 years

Secondary outcome [5]

Part 1 and 2: Disease Control Rate (DCR)

Timepoint [5]

Up to approximately 2 years

Secondary outcome [6]

Part 1 and 2: Progression Free Survival (PFS)

Timepoint [6]

Up to approximately 2 years

Secondary outcome [7]

Part 2: Number of Participants with SAEs

Timepoint [7]

Up to approximately 2 years

Secondary outcome [8]

Part 2: Number of Participants with TEAEs

Timepoint [8]

Up to approximately 2 years

Secondary outcome [9]

Part 2: Number of Participants with AESIs

Timepoint [9]

Up to approximately 2 years

Secondary outcome [10]

Part 2: Number of Participants with Interruptions to Dosing with BGB-3245

Timepoint [10]

Up to approximately 2 years

Secondary outcome [11]

Part 2: Number of Participants with Reductions in Dosing with BGB-3245

Timepoint [11]

Up to approximately 2 years

Eligibility

Key inclusion criteria

Key

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

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

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.

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Other

Other design features

Phase

Phase 1

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

18/04/2024

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

24/05/2027

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,VIC

Recruitment hospital [1]

Westmead Hospital - Westmead

Recruitment hospital [2]

Peter MacCallum Cancer Centre - Melbourne

Recruitment postcode(s) [1]

2145 - Westmead

Recruitment postcode(s) [2]

3000 - Melbourne

Recruitment outside Australia

Country [1]

United States of America

State/province [1]

California

Country [2]

United States of America

State/province [2]

North Carolina

Country [3]

United States of America

State/province [3]

Virginia

Funding & Sponsors

Primary sponsor type

Commercial sector/Industry

Name

MapKure, LLC

Address

Country

Ethics approval

Ethics application status

Summary

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.

Trial website

https://clinicaltrials.gov/ct2/show/NCT06194877

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Contact person for public queries

Name

MapKure

Address

Country

Phone

1-877-828-5568

Fax

clinicaltrials@mapkure.com

Contact person for scientific queries

Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06194877

Trial Review

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06194877