BI-1910 + Pembrolizumab for Solid Tumors

Recruiting at 11 trial locations

Overseen By Mona Welschof, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioInvent International AB

Must not be taking: Corticosteroids, Chemotherapy, Immunotherapy, others

Disqualifiers: CNS metastases, Autoimmune disease, HIV, others

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

Compensation: Varies

Number of Visits: 12

104 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had chemotherapy, small molecule anti-cancer therapy, or immunotherapy within 4 weeks before starting the trial, and there are specific washout periods for other treatments like radiotherapy.

What data supports the effectiveness of the drug pembrolizumab for treating solid tumors?

Pembrolizumab has shown effectiveness in treating various solid tumors, including non-small cell lung cancer and melanoma, by improving survival rates and achieving tumor responses. It works by helping the immune system attack cancer cells more effectively. ^{1 2 3 4 5}

What safety information is available for Pembrolizumab (Keytruda) in humans?

Pembrolizumab (Keytruda) has been associated with some side effects, including fatigue, cough, nausea, skin rash, and diarrhea. More serious immune-related side effects can occur, such as inflammation of the lungs (pneumonitis), liver (hepatitis), or intestines (colitis), and issues with hormone glands like the thyroid. ^{1 2 3 4 6}

What makes the drug combination BI-1910 and Pembrolizumab unique for treating solid tumors?

The combination of BI-1910 and Pembrolizumab is unique because Pembrolizumab is a PD-1 inhibitor that helps the immune system attack cancer cells, and it is being explored in combination with other drugs like BI-1910 to potentially enhance its effectiveness in solid tumors, which may not respond well to existing treatments. ^{1 2 6 7 8}

What is the purpose of this trial?

The goal of this first in human clinical trial is to test BI-1910 administered as single agent and in combination with pembrolizumab in subjects with advanced/metastatic solid tumors whose disease has progressed after standard therapy. The main questions it aims to answer are: * how safe and tolerable is BI-1910 * what is maximum tolerated or administrated dose * to determine recommended dose for further clinical trials Participants will receive infusions of BI-1910 alone or combination with pembrolizumab every 3 weeks.

Research Team

Andres McAllister, PhD

Principal Investigator

BioInvent International AB

Eligibility Criteria

This trial is for adults over 18 with advanced solid tumors, like liver or lung cancer, who've tried standard treatments without success. They should be relatively healthy otherwise (good organ function and physical condition) and have a life expectancy of at least 12 weeks.

Inclusion Criteria

My organ functions are within normal ranges according to recent tests.

You have at least one disease that can be measured according to specific guidelines.

You are able to understand and agree to participate in the trial by signing a form.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Phase 1 Part A - Dose Escalation

Dose escalation of BI-1910 as a single agent to evaluate safety and tolerability and to determine the recommended phase 2 dose (RP2D) as a single agent

21 days

Every 3 weeks

Phase 1 Part B - Dose Escalation

Dose escalation of BI-1910 in combination with pembrolizumab to evaluate safety and tolerability and to determine the recommended phase 2 dose (RP2D) for the combination

42 days

Every 3 weeks

Phase 2a Part A - Dose Expansion

BI-1910 administered as a single agent at the hypothesized recommended phase 2 dose determined in Phase 1

Up to 2 years

Every 3 weeks

Phase 2a Part B - Dose Expansion

BI-1910 administered in combination with pembrolizumab at the respective hypothesized recommended phase 2 doses determined in Phase 1

Up to 2 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Treatment Details

Interventions

• BI-1910
• Pembrolizumab

Trial Overview The trial tests BI-1910 alone or combined with Pembrolizumab in patients with advanced cancers. It aims to find the safest dose, how well people can handle it, and set recommendations for future trials. Treatments are given via infusion every three weeks.

Participant Groups

Group I: Phase I, Part B - Dose escalation and safety of BI-1910 in combination with pembrolizumab Experimental Treatment 2 Interventions

Dose escalation of BI-1910 in combination with pembrolizumab.

Group II: Phase I, Part A - Dose escalation and safety of BI-1910 as single agent Experimental Treatment 1 Intervention

Dose escalation of BI-1910 administered as a single agent.

Group III: Phase 2a, Part B - Dose expansion of BI-1910 Experimental Treatment 2 Interventions

BI-1910 administered in combination with pembrolizumab at the respective hypothesized recommended phase 2 doses determined in Phase 1

Group IV: Phase 2a, Part A - Dose expansion of BI-1910 as single agent Experimental Treatment 1 Intervention

BI-1910 administered as a single agent at the hypothesized recommended phase 2 dose determined in Phase 1.

Who Is Running the Clinical Trial?

BioInvent International AB

Lead Sponsor

Trials

19

Recruited

2,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

Pembrolizumab is an effective monoclonal antibody that targets the PD-1 immune checkpoint, helping to restore T cell anti-tumor responses, and is administered at a dose of 200 mg every 3 weeks until disease progression or for up to 24 months.

It has received approval for treating various cancers, including melanomas and non-small cell lung cancers, particularly in tumors that are hypermutated or express PD-L1, but ongoing research aims to expand its use to less immunogenic tumor types through combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. du Rusquec, P., de Calbiac, O., Robert, M., et al.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

3. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

Pembrolizumab: first global approval. [2021]

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

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022]

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

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. [2023]