BI-1808 + Pembrolizumab for Advanced Cancer

Recruiting at 15 trial locations

Overseen By Mona Welschof, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioInvent International AB

Must be taking: Anti-PD-1 therapy

Must not be taking: Immunosuppressants, Chemotherapy

Disqualifiers: CNS metastases, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 12

176 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called BI-1808 for individuals with advanced cancers, including certain solid tumors and T-cell lymphoma (TCL). Researchers aim to assess its safety, tolerability, and the optimal dose when used alone or with pembrolizumab, an immunotherapy. Participants will receive infusions every three weeks. Those whose cancer has progressed after standard treatments might be suitable candidates. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that you should not have received chemotherapy, immunotherapy, or certain other treatments within a few weeks before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that BI-1808, when used alone, is generally safe. Early studies indicate that patients with advanced solid tumors and T-cell lymphomas tolerate it well. No major safety issues have been reported, and it has effectively managed these conditions.

When combined with pembrolizumab, a treatment already approved for other uses, BI-1808 also appears safe. Tests have assessed the body's reaction and potential new side effects. So far, this combination has maintained a good safety record, with no serious side effects in most patients.

Overall, evidence suggests that both BI-1808 alone and with pembrolizumab are generally safe and well-tolerated in these studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI-1808 and pembrolizumab for advanced cancer because of their unique approach to treatment. Unlike most standard treatments, which often focus broadly on killing cancer cells, BI-1808 specifically targets a protein called TNFR2, which is thought to play a role in suppressing the immune system's ability to fight cancer. This targeted action could potentially lead to fewer side effects and better outcomes. Additionally, when combined with pembrolizumab, a well-known immune checkpoint inhibitor, there's hope that this duo could unleash a more powerful immune response against tumors, offering new hope for patients with advanced cancers.

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

Research has shown that BI-1808 demonstrates early signs of effectiveness, particularly for cutaneous T-cell lymphoma, a type of skin cancer. It targets TNFR2, potentially enhancing the body's ability to combat tumors. The treatment has appeared safe so far. In this trial, some participants will receive BI-1808 alone, while others will receive it in combination with pembrolizumab, a known cancer treatment that could further strengthen the immune system. The FDA has granted BI-1808 a fast track designation, indicating hope for its potential benefits. ^{1 2 3 4 6}

Who Is on the Research Team?

Andres McAllister, PhD

Principal Investigator

BioInvent International AB

Are You a Good Fit for This Trial?

Adults over 18 with advanced malignancies, including solid tumors and specific types of cutaneous T-cell lymphoma (CTCL), who have not responded to standard cancer treatments. Participants must be able to provide consent, have a life expectancy of at least 12 weeks, an ECOG performance status of 0-1, and measurable disease lesions. Specific criteria apply for NSCLC and OC patients regarding prior therapies.

Inclusion Criteria

I have a tumor that can be measured and biopsied safely.

My cancer has high PD-L1 and I've had anti-PD-1 therapy.

My cancer has low or unknown PD-L1 and I've had standard chemo and anti PD-1/PD-L1 therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Part A - Dose Escalation

Dose escalation of BI-1808 as a single agent to evaluate safety and tolerability and to determine the recommended Phase 2 dose (RP2D) as a single agent

Up to 104 weeks

Every 3 weeks

Phase 1 Part B - Dose Escalation

Dose escalation of BI-1808 in combination with pembrolizumab to evaluate safety and tolerability and to determine the recommended Phase 2 dose (RP2D) for the combination

Up to 104 weeks

Every 3 weeks

Phase 2a Part A - Dose Expansion

BI-1808 administered as a single agent at the hypothesized recommended Phase 2 dose determined in Phase 1

Up to 104 weeks

Every 3 weeks

Phase 2a Part B - Dose Expansion

BI-1808 administered in combination with pembrolizumab at the respective hypothesized recommended Phase 2 doses determined in Phase 1

Up to 104 weeks

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years and 90 days

What Are the Treatments Tested in This Trial?

Interventions

• BI-1808
• Pembrolizumab

Trial Overview The trial is testing BI-1808 alone and combined with Pembrolizumab in patients whose cancers have progressed after standard therapy. It's a multi-phase study assessing the safety and efficacy of these drugs in treating various advanced malignancies.

How Is the Trial Designed?

Group I: Phase I, Part B - Dose escalation and Safety of BI-1808 in combination with pembrolizumab Experimental Treatment 2 Interventions

Dose escalation of BI-1808 in combination with pembrolizumab.

Group II: Phase I, Part A - Dose escalation and safety of BI-1808 as single agent Experimental Treatment 1 Intervention

Dose escalation of BI-1808 administrated a single agent

Group III: Phase 2a, Part B - Dose expansion of BI-1808 in combination with pembrolizumab Experimental Treatment 2 Interventions

BI-1808 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-1808 as a single agent Experimental Treatment 1 Intervention

BI-1808 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 the KEYNOTE-024 study involving 305 patients with untreated advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival (OS) compared to platinum-based chemotherapy, with a median OS of 30.0 months versus 14.2 months for chemotherapy.

Pembrolizumab also had a better safety profile, with fewer treatment-related severe adverse events (31.2% for pembrolizumab vs. 53.3% for chemotherapy), indicating it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

In a phase 3 trial involving 834 patients with advanced melanoma, pembrolizumab demonstrated superior overall survival compared to ipilimumab, with a median overall survival not reached for either pembrolizumab group versus 16 months for ipilimumab.

The 24-month overall survival rate was 55% for both pembrolizumab dosing schedules (every 2 weeks and every 3 weeks), compared to 43% for ipilimumab, supporting pembrolizumab as a standard treatment for advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Schachter, J., Ribas, A., Long, GV., 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]

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 (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, 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) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[2021]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[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]

Citations

1. bioinvent.com bioinvent.com/en/press/bioinvent-announces-additional-positive-efficacy-data-single-agent-bi-1808-phase-2a-anti

BioInvent Announces Additional Positive Efficacy Data with ... In May 2024, promising early signs of BI-1808 single agent efficacy and a robust safety profile were announced. The data was presented in a ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04752826

Study Details | NCT04752826 | BI-1808 As a Single Agent ... This is a Phase 1/2a, dose-escalation, multicenter, first-in-human, consecutive-cohort, open-label study of BI-1808, as a single agent and in combination with ...

3. onclive.com onclive.com/view/fda-grants-fast-track-designation-to-bi-1808-in-select-cutaneous-t-cell-lymphoma

FDA Grants Fast Track Designation to BI-1808 in Select ... BI-1808 targets TNFR2, showing potential in enhancing antitumor activity, especially when combined with PD-1 inhibitors like pembrolizumab. The ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2641

19-BI-1808-01, a phase 1/2a clinical trial of BI- ... At doses of ≥ 675 mg Q3W, BI-1808 t½ was approximately one week leading to accumulation of drug, leading to complete receptor occupancy ...

5. biospace.com biospace.com/press-releases/bioinvent-presents-additional-ctcl-phase-2a-data-for-bi-1808-monotherapy-at-eha-2025

BioInvent Presents Additional CTCL Phase 2a Data for BI ... BI-1808 has shown single agent activity and excellent tolerability in an ongoing Phase 2a study and signs of efficacy and favorable safety ...

6. hra.nhs.uk hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/bi-1808-as-a-single-agent-and-with-pembrolizumab-in-treatment-of-advanced-malignancies/

BI-1808 as a single agent and with pembrolizumab in ... Data shows that a specific receptor called tumour necrosis factor 2 (TNFR2) is highly involved in this regulation. BI-1808 is a fully-human immunoglobulin ...