BI-1206 + Pembrolizumab for Advanced Cancer

Recruiting at 7 trial locations

Overseen By Andres McAllister, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BioInvent International AB

Must be taking: Anti-PD-1/PD-L1 therapy

Must not be taking: Corticosteroids, Immunotherapy

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: 6

197 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with advanced cancers that no longer respond to certain previous therapies. Researchers aim to determine if combining BI-1206, an experimental antibody, with Pembrolizumab, a drug that aids the immune system in fighting cancer, is safe and effective. It targets those with solid tumors who have already tried treatments targeting PD-1 or PD-L1 proteins. If previous treatments were ineffective and measurable disease lesions are present, this trial might be suitable. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had chemotherapy, small molecule products, or immunotherapy within 4 weeks of starting the trial. Additionally, you cannot take more than 10 mg of prednisolone daily or similar corticosteroids.

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

Research has shown that combining BI-1206 with pembrolizumab yields promising results in early studies. Initial data suggests this combination might be safe. In early testing, individuals with solid tumors tolerated the treatment well without major issues.

Pembrolizumab alone is already approved for treating other cancers and has undergone extensive study. It is generally well-tolerated, with manageable side effects for most people.

Overall, while early results are encouraging, further testing is necessary to confirm the treatment's safety and effectiveness. Participants should feel hopeful about the early findings but should also consult their doctor about any concerns before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BI-1206 in combination with Pembrolizumab for advanced cancer because it offers a fresh approach by targeting the CD32b receptor, which plays a crucial role in regulating immune responses. This is different from standard treatments like chemotherapy or other immunotherapies that target PD-1 alone. By potentially enhancing the effectiveness of Pembrolizumab, a well-established anti-PD-1 therapy, BI-1206 could improve patient outcomes by boosting the immune system's ability to fight cancer more effectively. Such a combination could also offer a new option for patients who have not responded well to existing therapies, providing hope for better management of their condition.

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

Research has shown that combining BI-1206 with pembrolizumab, the treatment under study in this trial, may help combat advanced solid tumors. Early studies suggest that BI-1206 enhances the immune system's ability to recognize and attack cancer cells. Pembrolizumab, a well-known cancer treatment, has improved outcomes, particularly in cancers with markers like high PD-L1 levels. Together, these treatments aim to enhance each other's effectiveness, offering hope for patients whose cancer hasn't responded to other treatments. Initial results are promising, showing positive effects in patients who have already tried other therapies. ^{1 2 5 6 7}

Who Is on the Research Team?

Carneiro, PhD

Principal Investigator

Lund University Hospital

Are You a Good Fit for This Trial?

Adults with advanced solid tumors who've had at least two doses of anti-PD-1/L1 therapy and disease progression within 12 weeks after the last dose. They must have measurable disease, a life expectancy over 12 weeks, good organ function, and be able to consent. Exclusions include active brain metastases, severe pneumonitis history, high steroid needs, pregnancy or breastfeeding women, recent major surgery recovery patients, high medical risk due to systemic diseases including infections or graft versus host disease.

Inclusion Criteria

I have metastatic melanoma and have been treated with anti-PD-1 therapy, and if applicable, BRAF-targeted therapy.

Is willing and able to provide written informed consent for the trial.

I can safely have a biopsy before starting BI-1206 treatment.

Exclusion Criteria

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

I need more than 10 mg of prednisolone or a similar medication daily.

I have AL amyloidosis affecting my heart or kidneys.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Dose-finding with BI-1206 in combination with pembrolizumab, assessing IV or SC dosing and selecting the RP2D

6 weeks

3 visits (in-person)

Phase 2a Treatment

3 expansion cohorts at the scRP2D for subjects treated with pembrolizumab and BI-1206, with additional cycles every 3 weeks for up to 2 years

Up to 2 years

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• BI-1206
• Pembrolizumab

Trial Overview The trial is testing BI-1206 in combination with Pembrolizumab for those whose tumors progressed after anti-PD-1/L1 treatment. It's a Phase 1/2a study focusing on safety and effectiveness across different cohorts based on tumor type and previous treatments.

How Is the Trial Designed?

Group I: BI-1206 + Pembrolizumab 25mg/mL (MK-3475) Experimental Treatment 1 Intervention

BI-1206 administrated either IV or SC + Pembrolizumab 200mg administered IV every third week as a fixed dose will be used.

BI-1206 is already approved in United States, China, European Union for the following indications:

Approved in United States as BI-1206 for:

• Orphan designation for Follicular lymphoma and Mantle-cell lymphoma

Approved in China as BI-1206 for:

• Under clinical trial for Indolent B-Cell Non-Hodgkin Lymphoma

Approved in European Union as BI-1206 for:

• Under clinical trial for Indolent B-Cell Non-Hodgkin Lymphoma

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-189 study involving 616 patients with metastatic non-squamous non-small-cell lung cancer, the combination of pembrolizumab and pemetrexed-platinum significantly maintained quality of life (GHS/QOL) scores compared to placebo, with a notable improvement at week 21.

Patients receiving pembrolizumab also experienced a longer median time to deterioration in symptoms like cough and chest pain, although this result was not statistically significant, indicating potential benefits in symptom management with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes following pembrolizumab or placebo plus pemetrexed and platinum in patients with previously untreated, metastatic, non-squamous non-small-cell lung cancer (KEYNOTE-189): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Garassino, MC., Gadgeel, S., Esteban, E., et al.[2020]

Pembrolizumab (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[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 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, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

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) 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 (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

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-announces-promising-phase-1-data-bi-1206-combination-keytrudar-pembrolizumab-solid

BioInvent Announces Promising Phase 1 Data of BI-1206 ... The Phase 1 dose escalation has been completed, and results show encouraging early signs of clinical activity in solid tumors with one ...

2. bioinvent.com bioinvent.com/en/clinical-programs/our-programs/bi-1206pembrolizumab

BI-1206/pembrolizumab BI-1206 is developed to re-establish the clinical effect of existing cancer treatments such as pembrolizumab. The upcoming Phase 2a study of BI-1206 in ...

3. keytrudahcp.com keytrudahcp.com/efficacy/

Efficacy Data for KEYTRUDA® (pembrolizumab) Health care professionals may review efficacy data for KEYTRUDA® (pembrolizumab), browse the indications and select the corresponding KEYNOTE trials for ...

4. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/88/NCT03267888/Prot_SAP_001.pdf

Pembrolizumab (MK-3475, IND 130757) INVESTIGATORS While outcomes have improved with the introduction of new agents, patients continue to relapse after effective therapy, and ultimately develop refractory ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11117617/

A Systematic Review and Meta-Analysis Pembrolizumab significantly enhances clinical outcomes in metastatic cervical cancer, particularly among patients with high PD-L1 expression. The drug maintains ...

6. finance.yahoo.com finance.yahoo.com/news/bioinvent-announces-promising-phase-1-062000959.html

BioInvent Announces Promising Phase 1 Data of BI-1206 ... The Phase 1 dose escalation has been completed, and results show encouraging early signs of clinical activity in solid tumors with one ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01295827

NCT01295827 | Study of Pembrolizumab (MK-3475) in ... The study will investigate the safety, tolerability, and efficacy of pembrolizumab (2 mg/kg and 10 mg/kg) in participants with advanced or metastatic MEL.