BGB-3245 + Panitumumab for Colorectal Cancer

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

13 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Panitumumab for colorectal cancer?

Panitumumab has been shown to help patients with a specific type of colorectal cancer live longer without their cancer getting worse, especially when other treatments have failed. It works best for patients whose tumors have a normal KRAS gene, and it is often used when the cancer has spread to other parts of the body. ^{1 2 3 4 5}

Is the combination of BGB-3245 and Panitumumab safe for humans?

Panitumumab (Vectibix) has been used in treating colorectal cancer, but it can cause side effects like skin rash, low magnesium levels, and digestive issues. Serious side effects include lung problems, severe skin reactions, and infusion reactions. There is no specific safety data available for BGB-3245 in humans. ^{1 2 3 4 6}

What makes the drug BGB-3245 + Panitumumab unique for colorectal cancer?

BGB-3245 + Panitumumab is unique because it combines a novel investigational drug, BGB-3245, with Panitumumab, a targeted therapy that specifically binds to the epidermal growth factor receptor (EGFR) on cancer cells, potentially offering a new approach for treating colorectal cancer by targeting specific pathways involved in tumor growth. ^{7 8 9 10 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Panitumumab]. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Panitumumab (vectibix). [2021]

3. United States 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. [2020]

4. England pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: panitumumab (Vectibix). [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. England pubmed.ncbi.nlm.nih.gov

FDA review of a panitumumab (Vectibix) clinical trial for first-line treatment of metastatic colorectal cancer. [2018]

7. England 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. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma. [2020]

9. United States 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. [2021]

10. England pubmed.ncbi.nlm.nih.gov

The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma. [2023]

11. New Zealand 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. [2022]