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

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, 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.

What data supports the effectiveness of the drug pembrolizumab in treating advanced cancer?

Pembrolizumab has been shown to improve survival in patients with advanced non-small cell lung cancer and melanoma, as it helps the immune system attack cancer cells more effectively. Studies have demonstrated that patients receiving pembrolizumab had better outcomes compared to those receiving traditional chemotherapy. ^{1 2 3 4 5}

Is the combination of BI-1808 and Pembrolizumab safe for humans?

Pembrolizumab (also known as KEYTRUDA or MK-3475) has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and more serious immune-related issues like pneumonitis (lung inflammation) and thyroid problems. While specific safety data for BI-1808 is not provided, pembrolizumab's safety profile is well-documented in other cancer treatments. ^{1 2 6 7 8}

What makes the drug BI-1808 + Pembrolizumab unique for advanced cancer?

The combination of BI-1808 and Pembrolizumab is unique because it combines a new treatment (BI-1808) with Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells. Pembrolizumab has shown effectiveness in various cancers, and this combination may offer a novel approach for advanced cancer by potentially enhancing the immune response. ^{1 2 4 9 10}

What is the purpose of this trial?

The goal of this first in human clinical trial is to test BI-1808 administered as single agent and in combination with pembrolizumab in subjects with advanced malignancies whose disease has progressed after standard therapy. The main questions it aims to answer are: * how safe and tolerable is BI-1808 * what is maximum tolerated or administrated dose * to determine recommended dose for further clinical trials. Participants will receive infusions of BI-1808 alone or combination with pembrolizumab every 3 weeks. For the purpose of this study, subjects with advanced malignancies includes subjects with advanced solid tumors and subjects with T-cell lymphoma (TCL),

Research Team

Andres McAllister, PhD

Principal Investigator

BioInvent International AB

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. 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]

3. United States 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. [2022]

4. 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]

5. England 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). [2022]

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

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

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

New Approved Use for Keytruda. [2022]