BGB-3245 + Panitumumab for Colorectal Cancer

No longer recruiting at 4 trial locations

Overseen By MapKure

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: MapKure, LLC

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Active infection, Cardiovascular disease, Pneumonitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, BGB-3245 (also known as Brimarafenib) and panitumumab, for individuals with advanced colorectal cancer. The main goal is to determine the safety of this combination and identify the best dose for future studies. Researchers aim to assess how effectively these drugs work together in shrinking tumors. Ideal participants are those whose colorectal cancer has worsened despite other treatments and who have a specific gene mutation in their cancer. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial requires that you stop taking any strong CYP3A4 inhibitors or inducers at least 14 days before starting the study treatment. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research is examining the safety and tolerability of combining BGB-3245 with panitumumab for colorectal cancer treatment. Earlier studies have focused on patient tolerance and potential side effects of this combination.

Currently, the trials are in the early stages, primarily assessing the treatment's safety. Researchers monitor for any health changes, known as adverse effects, that might occur during the study. Although specific information on side effects is limited, early trials like this prioritize ensuring the treatment does not cause serious harm.

So far, participants have generally tolerated BGB-3245 with panitumumab well. However, potential side effects are closely monitored, as with any new treatment. Ongoing studies are essential to fully understand the safety of this combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of BGB-3245 and panitumumab for colorectal cancer because it targets specific genetic mutations, like KRAS and NRAS, which are often difficult to treat with existing therapies. Most standard treatments for colorectal cancer, like chemotherapy and targeted therapies such as cetuximab, focus broadly on cancer cells, but this combination homes in on specific oncogenic mutations, potentially improving effectiveness. BGB-3245 is a unique molecule that works by inhibiting the MAPK pathway, which is crucial for cancer cell growth, while panitumumab is an antibody that targets the EGFR receptor. This dual approach could offer a more precise attack on cancer cells, potentially leading to better outcomes for patients who have not responded to previous treatments.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

Research has shown that using BGB-3245 with panitumumab may help treat advanced colorectal cancer. In this trial, participants will receive this combination to target specific gene changes that often cause cancer to grow. For patients with these gene changes, the treatment was linked to a median time of 6.9 months without cancer progression. This indicates that patients lived longer without their cancer worsening. While more research is needed, these early findings suggest it could help control the disease. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced colorectal or pancreatic ductal cancers that have worsened after at least one treatment. They must be in good physical condition, have proper organ and blood function, and their tumors should have specific mutations (BRAF, KRAS, NRAS). Participants need to provide a tumor sample for analysis.

Inclusion Criteria

My blood and organ tests meet the required health standards.

My heart is functioning well.

I can provide a sample of my tumor for testing.

Exclusion Criteria

History of corneal perforation, keratitis, or severe dry eye

I do not have an active infection needing treatment when the study starts.

My side effects from previous treatments are mild or stable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

Participants receive escalating doses of BGB-3245 in combination with panitumumab to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) by assessing safety, tolerability, preliminary antitumor activity, and pharmacokinetics (PK)

8-12 weeks

Dose Expansion

Participants receive the RP2D of BGB-3245 in combination with panitumumab to further evaluate safety, PK, and assess preliminary antitumor activity

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BGB-3245
• Panitumumab

Trial Overview The study tests the combination of BGB-3245 (brimarafenib) and panitumumab on patients with certain cancer mutations. It aims to find the safest dose mix (Part 1) and then measure how well tumors respond to this combo at that dose (Part 2), using standard response criteria.

How Is the Trial Designed?

Group I: Part 2: Dose Expansion Part, Group 2 Experimental Treatment 2 Interventions

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.

Group II: Part 2: Dose Expansion Part, Group 1 Experimental Treatment 2 Interventions

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.

Group III: Part 1: Dose Finding Part Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

MapKure, LLC

Lead Sponsor

Trials

2

Recruited

170+

Published Research Related to This Trial

Panitumumab is a human monoclonal antibody that targets the epidermal growth factor receptor (EGFR), which plays a crucial role in the growth and spread of cancer cells, specifically in metastatic colorectal carcinoma.

It is used as a single-agent treatment for patients whose cancer has progressed after standard chemotherapy regimens, including fluoropyrimidine, oxaliplatin, and irinotecan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab (vectibix). Gemmete, JJ., Mukherji, SK.[2021]

Panitumumab (Vectibix) was evaluated in a trial with 463 patients suffering from advanced colorectal cancer, showing a mean progression-free survival (PFS) of 96 days compared to 60 days for those receiving only best supportive care, indicating a significant benefit in delaying disease progression.

Despite the improvement in PFS and an objective response rate of 8%, there was no difference in overall survival between the treatment groups, leading to accelerated approval by the FDA with the requirement for further confirmation of clinical benefit for full approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Giusti, RM., Shastri, K., Pilaro, AM., et al.[2020]

A clinical trial showed that adding panitumumab to bevacizumab and chemotherapy for first-line treatment of metastatic colorectal cancer resulted in worse progression-free survival and increased toxicity compared to bevacizumab and chemotherapy alone.

Patients receiving panitumumab experienced a higher incidence of severe adverse events (87% vs. 72%) and a greater risk of death (9% vs. 4%), leading to the conclusion that panitumumab should not be recommended in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA review of a panitumumab (Vectibix) clinical trial for first-line treatment of metastatic colorectal cancer. Giusti, RM., Cohen, MH., Keegan, P., et al.[2018]

Panitumumab, when combined with chemotherapy, significantly prolongs progression-free survival in patients with wild-type KRAS metastatic colorectal cancer, but shows no overall survival benefit in second-line treatment.

In patients with mutant KRAS tumors, panitumumab is less effective, leading to shorter progression-free survival compared to chemotherapy alone, highlighting the importance of KRAS mutation status in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab: a review of its use in metastatic colorectal cancer. Keating, GM.[2021]

Panitumumab (Vectibix) is approved for treating metastatic colorectal cancer specifically in patients with EGFR-expressing tumors that have non-mutated K-ras genes after standard chemotherapy has failed.

In a phase III study, patients receiving panitumumab along with best supportive care experienced significantly longer progression-free survival compared to those who only received best supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Panitumumab]. Musch, A.[2018]

Polatuzumab vedotin, an antibody-drug conjugate targeting CD79b, has demonstrated significant clinical effectiveness in treating follicular and diffuse large B-cell lymphoma (DLBCL), and is FDA-approved for use with bendamustine and rituximab in patients with relapsed or refractory DLBCL.

The review highlights the ongoing research and potential future applications of polatuzumab in the treatment of B-cell non-Hodgkin lymphoma, indicating its importance in expanding treatment options for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profile of Polatuzumab Vedotin in the Treatment of Patients with Relapsed/Refractory Non-Hodgkin Lymphoma: A Brief Report on the Emerging Clinical Data. Sawalha, Y., Maddocks, K.[2022]

Panitumumab, approved for treating metastatic colorectal cancer, significantly improved progression-free survival (PFS) compared to best supportive care alone, with median PFS times of 56 days versus 51 days, respectively, in a study of 463 patients.

While panitumumab showed efficacy in delaying disease progression, it did not improve overall survival, and common side effects included skin rash and hypomagnesemia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: panitumumab (Vectibix). Giusti, RM., Shastri, KA., Cohen, MH., et al.[2018]

In pivotal study GO29365 involving patients with relapsed/refractory diffuse large B-cell lymphoma, polatuzumab vedotin (1.8 mg/kg) combined with bendamustine-rituximab showed a favorable risk/benefit profile, supporting its use for six cycles.

Supportive studies indicated that higher exposure to polatuzumab vedotin increased response rates but also raised the risk of side effects like peripheral neuropathy and anemia, suggesting that dosing should not fall below 1.8 mg/kg to maintain efficacy while managing safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-safety and exposure-efficacy analyses of polatuzumab vedotin in patients with relapsed or refractory diffuse large B-cell lymphoma. Lu, T., Gibiansky, L., Li, X., et al.[2021]

The study determined that the recommended phase II dose (RP2D) of voxtalisib, when combined with rituximab or rituximab plus bendamustine, is 50 mg taken twice daily, with an acceptable safety profile observed in 37 patients.

Voxtalisib showed promising anti-tumor activity, with 11.4% of patients achieving a complete response and 37.1% achieving a partial response, indicating potential efficacy in treating relapsed or refractory B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib trial of the PI3K/mTOR inhibitor voxtalisib (SAR245409) in combination with chemoimmunotherapy in patients with relapsed or refractory B-cell malignancies. Awan, FT., Gore, L., Gao, L., et al.[2021]

The study evaluated the antibody-drug conjugate polatuzumab vedotin (pola) combined with rituximab/obinutuzumab and chemotherapy in treating B-cell non-Hodgkin lymphoma, showing that pola's pharmacokinetics were consistent and dose-proportional across different treatment cycles.

There were no significant drug-drug interactions between pola and the chemotherapy regimen (R/G-CHP), indicating that pola can be safely used in combination with these treatments for previously untreated diffuse large B-cell lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma. Shemesh, CS., Agarwal, P., Lu, T., et al.[2020]

In a phase I trial involving 23 patients with metastatic urothelial carcinoma, the combination of sacituzumab govitecan (SG) and enfortumab vedotin (EV) demonstrated a high objective response rate of 70%, with three patients achieving complete responses.

The study identified a safe dose for further testing, with 78% of patients experiencing grade ≥3 adverse events, indicating that while the treatment is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma. McGregor, BA., Sonpavde, GP., Kwak, L., et al.[2023]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-03044

A Study to Investigate BGB-3245 (Brimarafenib) With ... Assess the safety and tolerability of the combination of BGB-3245 and panitumumab in participants with advanced or metastatic colorectal cancer (CRC)

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11506008/

KRAS, a New Target for Precision Medicine in Colorectal ... Additionally, the therapeutic combination was associated with a median progression-free survival of 6.9 months, suggesting potential improvement ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06194877?tab=history&a=1

Record History | ver. 1: 2023-12-22 | NCT06194877 The date on which summary results information was first available on ClinicalTrials.gov with quality control review comments from the National Library of ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT06194877

A Study to Investigate BGB-3245 (Brimarafenib) With ... A Phase 1b trial evaluating brimarafenib (BGB-3245) in adult patients with RAF mutant solid tumors is ongoing; additional data from the dose expansion portion ...

5. australianclinicaltrials.gov.au australianclinicaltrials.gov.au/anzctr-search-results?condition_category=all&condition_code=all&ethics_approval=No&gender=all&healthy_volunteers=all&phase=all&purpose_of_study=all&recruitment_sites=all&recruitment_status=all&search_text=&page=291

ANZCTR search results | Australian Clinical ... A Study to Investigate BGB-3245 (Brimarafenib) With Panitumumab in Participants With Advanced or Metastatic RAS Mutant Colorectal and Pancreatic Ductal Cancers.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06194877?tab=history&a=2

Record History | ver. 2: 2024-03-20 | NCT06194877 An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

7. delta.larvol.com delta.larvol.com/Products/?ProductId=f5e053c7-92a6-43a6-9e98-083cac32292d

brimarefenib (BGB-3245) / MapKure, BeOne Medicines, ... EMA filing • P1 data • P2b data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Neurofibromatosis • Oncology • Pancreatic Cancer • Pancreatic ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12071034/

Targeting the KRAS Oncogene for Patients with Metastatic ... KRAS mutations occur in approximately 40% of colorectal cancer (CRC) cases. These mutations drive tumorigenesis through the constitutive ...