Combining BI-1206 with Pembrolizumab for Advanced Solid Tumors

A Phase 1/2a Clinical Trial of BI-1206, a Monoclonal Antibody to CD32b (FcγRIIB), in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

This study is testing a new combination of two treatments, BI-1206 and pembrolizumab, to see if it can help people with advanced solid tumors who have already tried other therapies.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 197 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: BioInvent International AB (Industry-sponsored)
• Drugs / interventions: pembrolizumab, chemotherapy, immunotherapy
• Locations: 25 sites (Los Angeles, California and 24 other locations)
• Trial ID: NCT04219254 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of BI-1206, a monoclonal antibody targeting CD32b, in combination with pembrolizumab for patients with advanced solid tumors who have previously been treated with PD-1 or PD-L1 inhibitors. The trial is divided into two phases: Phase 1 focuses on determining the optimal dosing of BI-1206, while Phase 2a involves expansion cohorts for specific tumor types such as non-small-cell lung cancer and metastatic melanoma. Participants will receive a combination therapy for up to two years, depending on their response to treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed advanced solid tumors who have progressed after prior PD-1 or PD-L1 therapy.

Not a fit: Patients who have not received prior PD-1 or PD-L1 therapy or those with early-stage tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors who have limited treatment alternatives.

How similar studies have performed: Other studies combining immune checkpoint inhibitors have shown promising results, suggesting potential success for this novel combination approach.

Eligibility criteria

Inclusion Criteria:

* Is willing and able to provide written informed consent for the trial.
* Is ≥18 years of age on day of signing informed consent.
* Phase I only: Has a histologically confirmed advanced solid tumor. Subjects must have received at least 2 doses of an approved anti-PD-1/L1 mAb, and have documented progression on or within 12 weeks from the last dose of anti-PD-1/L1 mAb.
* For patients with NSCLC (phase 2A SC cohorts):

Have a histologically confirmed diagnosis of advanced or metastatic NSCLC and not have an EGFR sensitizing (activating) mutation or an ALK translocation.

Have a PD-L1 positive (TPS≥50%) tumor as determined by IHC at a local laboratory.

Have not received prior systemic immunotherapy or chemotherapy treatment for their advanced/metastatic NSCLC.

Have provided formalin-fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of advanced or metastatic disease has been made and from a lesion not previously irradiated to perform biomarker analysis.

• For patients with uveal melanoma (phase 2A SC cohort): Have a histologically confirmed diagnosis of advanced or metastatic uveal melanoma

Have a PD-L1 positive (TPS≥1%) tumor as determined by IHC at a local laboratory.

Have not received prior systemic immunotherapy or chemotherapy treatment for their advanced/metastatic uveal melanoma. Subjects who have received previous treatment with tebentafusp and/or liver directed therapy are allowed.

Have provided formalin-fixed tumor tissue sample from a biopsy of a tumor lesion either at the time of or after the diagnosis of advanced or metastatic disease has been made and from a site not previously irradiated to perform biomarker analysis.

* Phase I only: Is intolerant of, refuses, or is not eligible for standard antineoplastic therapy.
* Has at least 1 measurable disease lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
* Phase IIa only: Is willing to provide an archival tumor tissue sample or newly obtained \[core, incisional, OR excisional\] biopsy of a tumor lesion not previously irradiated.
* Is able to safely undergo a baseline tumor tissue biopsy prior to first dose of BI-1206.
* Has a life expectancy of ≥12 weeks.
* Has an ECOG performance status of 0-1.
* Has adequate organ function as confirmed by laboratory values listed in the main body of the protocol
* Phase IIa only: Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to enrolment
* Phase IIa only: Participants with history of HCV infection are eligible if HCV viral load is undetectable at Screening
* Phase IIa only: Has adequate hematological and biochemical indices as listed in the main body of the protocol

Exclusion Criteria:

* Needs doses of prednisolone \>10 mg daily (or equipotent doses of other corticosteroids) while on the study, other than as premedication.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has known or suspected hypersensitivity to pembrolizumab or BI-1206 or any of their excipients.
* Has cardiac or renal amyloid light-chain (AL) amyloidosis.
* Has received radiotherapy within 2 weeks of the first dose of BI-1206.
* Has not recovered from AEs to at least Grade 1 by CTCAE v5.0 (or higher) due to prior anticancer therapies• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
* Has an active, known or suspected autoimmune disease.
* Is a female subject and has the ability to become pregnant (or already pregnant or lactating/breastfeeding)
* Is a male subject with partner(s) of childbearing potential (unless he agrees to use a barrier method of contraception during the study and for 12 months after completing treatment)
* Has had major surgery from which the subject has not yet recovered Is at high medical risk because of non-malignant systemic disease, including severe active infections on treatment with antibiotics, antifungals, or antivirals
* Has presence of chronic graft-versus-host disease.
* Has had an allogenic tissue/solid organ transplant.
* Has a known history of HIV infection
* Has a history of active tuberculosis (Bacillus tuberculosis)
* Has received a live vaccine within 30 days before the first dose of study treatment
* Has uncontrolled or significant cardiovascular disease as listed in the main body of the protocol
* Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study
* 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 lead to participation not being in the best interest of the subject, in the opinion of the treating Investigator.
* Is participating or planning to participate in another interventional clinical study or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study drug
* Has a known additional malignancy of another type, with the exception of adequately treated cone-biopsied carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) and basal or squamous cell carcinoma of the skin
* Has a diagnosis of primary or acquired immunodeficiency disorder or has taken any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
* Is unable to attend the study site to receive the study treatment

Additional exclusion criteria are described in the protocol.

Where this trial is running

Los Angeles, California and 24 other locations

• University of California Los Angeles — Los Angeles, California, United States (Not_yet_recruiting)
• Sarah Cannon Research Institute — Denver, Colorado, United States (Completed)
• HealthPartners Institute - Regions Cancer Care Center, — Saint Paul, Minnesota, United States (Completed)
• Oklahoma University , Stephenson Cancer Center — Oklahoma City, Oklahoma, United States (Completed)
• NEXT Oncology — San Antonio, Texas, United States (Completed)
• LTD High Technology Hospital Med Center — Batumi, Georgia (Recruiting)
• Israel-Georgian Medical Research Clinic Helsicore — Tbilisi, Georgia (Terminated)
• Jerarsi Clinic — Tbilisi, Georgia (Recruiting)
• Medizinische Hochschule Hannover — Hanover, Germany (Not_yet_recruiting)
• Nationales Centrum für Tumorerkrankungen — Heidelberg, Germany (Not_yet_recruiting)
• Universität des Saarlandes — Homburg, Germany (Not_yet_recruiting)
• Maria Skłodowska-Curie National Institute of Oncology — Gliwice, Poland (Terminated)
• Medical University of Silesia — Katowice, Poland (Not_yet_recruiting)
• Instytut Centrum Zdrowia Matki Polki — Lodz, Poland (Recruiting)
• Institutul Oncologic "Prof. Dr. Ion Chiricuta" — Cluj-Napoca, Romania (Recruiting)
• Centrul de Oncologie SF Nectarie SRL — Craiova, Romania (Recruiting)
• Hospital Universitari Dexeus — Barcelona, Spain (Recruiting)
• Hospital Universitari Vall D´Hebron — Barcelona, Spain (Recruiting)
• Institut Català d'Oncologia Hospital Duran i Reynals — Barcelona, Spain (Recruiting)
• Hospital Puerta de Hierro — Majadahonda, Spain (Not_yet_recruiting)
• Clinica Universidad de Navarra — Pamplona, Spain (Recruiting)
• Hospital Virgen de la Macarena — Seville, Spain (Recruiting)
• Sahlgrenska University Hospital — Gothenburg, Sweden (Completed)
• Lund University Hospital — Lund, Sweden (Recruiting)
• Karolinska University Hospital, Solna — Stockholm, Sweden (Recruiting)

Study contacts

• Study coordinator: Philipp Zimmermann, Dr. rer. nat.

Conditions Solid Tumor, Adult