BI-1910 + Pembrolizumab for Solid Tumors

Not currently recruiting at 14 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called BI-1910, both alone and with pembrolizumab (an immunotherapy drug), for individuals with advanced or metastatic solid tumors that have worsened after standard treatments. The main goals are to assess the safety of BI-1910, determine patient tolerance, and identify the right dose for future studies. Participants will receive infusions every three weeks. The trial seeks individuals with a solid tumor, whose disease has progressed despite typical treatments, and who are willing to provide tumor samples. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

A previous study tested BI-1910 alone, and participants did not experience significant side effects, indicating it was generally safe. The study also examined the combination of BI-1910 with pembrolizumab, a drug commonly used in cancer treatments. Other studies have shown pembrolizumab to be safe. Overall, these findings suggest that both treatments are safe in the tested settings, making them promising options for further research in clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI-1910 and Pembrolizumab for solid tumors because they offer a fresh approach to tackling these challenging cancers. Unlike traditional chemotherapy that kills both cancerous and healthy cells, BI-1910 is designed to specifically target tumor cells, potentially minimizing side effects. Pembrolizumab, an immunotherapy drug, works by helping the body's immune system recognize and attack cancer cells more effectively. The combination of these two could enhance the immune response against tumors, offering hope for more effective treatment outcomes compared to current options like chemotherapy or single-agent immunotherapy.

What evidence suggests that this trial's treatments could be effective for advanced/metastatic solid tumors?

Research has shown that BI-1910, one of the treatments in this trial, produces promising results when used alone. In earlier studies, 6 out of 12 patients maintained stable disease, meaning their cancer did not worsen. The treatment was well-tolerated, with no major side effects reported. In this trial, some participants will receive BI-1910 as a single agent, while others will receive it combined with pembrolizumab. Pembrolizumab is already known to help the immune system fight cancer. Together, these treatments could offer a strong option for people with advanced solid tumors. ^{1 3 5 6 7}

Who Is on the Research Team?

Andres McAllister, PhD

Principal Investigator

BioInvent International AB

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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, 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]

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]

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 (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, 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]

Citations

1. bioinvent.com bioinvent.com/en/press/bioinvent-present-phase-1-clinical-data-bi-1910-tnfr2-agonist-treatment-solid-tumors-sitc

BioInvent to Present Phase 1 Clinical Data for BI-1910, a ... As previously reported, the single agent dose escalation of BI-1910 in the Phase 1 study was completed without any notable adverse events.

2. bioinvent.com bioinvent.com/en/press/bioinvent-announces-promising-data-bi-1910-single-agent-phase-1-study-solid-tumors-2291443

BioInvent announces promising data for BI-1910 as single ... Out of the 12 currently evaluable patients, 6 patients display stable disease. Early results indicate favorable pharmacokinetic data and a ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06205706

Study Details | NCT06205706 | BI-1910 as a Single Agent ... Phase 1 Part A consists of a dose escalation of BI-1910 as a single agent to evaluate safety and tolerability and to determine the RP2D as a single agent (sRP2D) ...

4. clinicaltrials.eu clinicaltrials.eu/inn/bi-1910/

Bi-1910 – Application in Therapy and Current Clinical ... This trial is for patients with advanced or metastatic solid tumors, including non-small cell lung cancer and hepatocellular carcinoma (liver cancer).

5. finance.yahoo.com finance.yahoo.com/news/bioinvent-present-phase-1-clinical-131500670.html

BioInvent to Present Phase 1 Clinical Data for BI-1910, a ... As previously reported, the single agent dose escalation of BI-1910 in the Phase 1 study was completed without any notable adverse events.

6. bioinvent.com bioinvent.com/en/clinical-programs/our-programs/bi-1910

BI-1910 During the first part of Phase 1/2a study the safety, tolerability, and potential signs of efficacy of BI-1910 as a single agent will be evaluated in patients ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02650-4/fulltext

1073TiP A phase I/IIa first in-human phase I study of BI ... We are developing BI-1910, an agonistic human IgG2 mAb targeting TNFR2. BI-1910 agonizes T cells and mediates CD4+ and CD8+ T cell activation.