BI-1910 as a Single Agent and in Combination With Pembrolizumab for the Treatment of Advanced Solid Tumors

NCT06205706 | Active Not Recruiting Phase 1 FDA Drug

• 4 other identifiers: 22-BI-1910-01U1111-1293-26342022-503066-74-00KEYNOTE F82
• Study Type: interventional
• Target: 35
• Locations: 4 countries
• Sites: 8

Brief Summary

The goal of this first in human clinical trial is to test BI-1910 administered as single agent and in combination with pembrolizumab in subjects with advanced/metastatic solid tumors whose disease has progressed after standard therapy. The main questions it aims to answer are:

• how safe and tolerable is BI-1910
• what is maximum tolerated or administrated dose
• to determine recommended dose for further clinical trials Participants will receive infusions of BI-1910 alone or combination with pembrolizumab every 3 weeks.

Conditions

Solid Tumors; Non Small Cell Lung Cancer; Hepatocellular Carcinoma

Keywords

solid tumors

Outcome Measures

Primary Outcomes (12)

• Occurrence of adverse events (AEs)

  AEs will be assessed by the investigators by severity and will be graded according to the NCI CTCAE v5.0 or higher and causality between AEs and the exposure to the study treatment.

  From the start of the study treatment for up to 2 years and 90 days.

• Occurrence of serious adverse events (SAEs)

  SAEs will be assessed by the investigators by severity and will be graded according to the NCI CTCAE v5.0 or higher and causality between SAEs and the exposure to the study treatment

  From screening for up to 28 days, throughout treatment for up to 2 years and through follow-up for up to 90 days

• Frequency of AEs leading to discontinuation of study treatment

  All adverse events leading to premature study treatment discontinuation will be analyzed descriptively utilizing corresponding MedDRA, System Organ Classes, and Preferred Terms.

  From screening for up to 28 days, throughout treatment for up to 2 years and through follow-up for up to 90 days

• Frequency of dose interruptions and dose reductions.

  Study treatment modifications will be summarized in 2 categories: dose reduction and dose interruptions. The number and percentage of subjects who have any dose reduction or interruption and have at least 1 dose reduction or interruption will be summarized. Lastly, the primary reason for each form of study treatment modification will also be summarized.

  From the start of the study treatment for up to 2 years

• Changes from baseline in laboratory parameters

  These include clinical laboratory assessments (hematology, clinical chemistry, urinalysis), additional CRP assessment, coagulation, thyroid, pregnancy, and viral serology assessments Safety laboratory results will be graded by NCI CTCAE v5.0 (or higher). If no grading exists, values will be classified into low/normal/high based on laboratory normal ranges. Each parameter will be presented by descriptive statistics at each visit, including change from baseline.

  From screening for up to 28 days, throughout treatment for up to 2 years and through follow-up for up to 90 days

• Changes from baseline in temperature (C or F)

  Temperature (C or F) will be measured in a seated or supine position after 5 minutes' rest and will be summarized by descriptive statistics at each visit, including change from baseline.

  From screening for up to 28 days, throughout treatment for up to 2 years and through follow-up for up to 90 days

• Changes from baseline in Respiratory Rate (Breaths/Min)

  Respiratory rate (breaths/min) will be measured in a seated or supine position after 5 minutes' rest and will be summarized by descriptive statistics at each visit, including change from baseline.

  From screening for up to 28 days, throughout treatment for up to 2 years and through follow-up for up to 90 days

• Changes from baseline in Blood Pressure (mmHg)

  Systolic and diastolic blood pressure (mmHg) will be measured in a seated or supine position after 5 minutes' rest and will be summarized by descriptive statistics at each visit, including change from baseline.

  From screening for up to 28 days, throughout treatment for up to 2 years and through follow-up for up to 90 days

• Changes from baseline in O2 Saturation (%)

  O2 Saturation (%) will be measured in a seated or supine position after 5 minutes' rest and will be summarized by descriptive statistics at each visit, including change from baseline.

  From screening for up to 28 days, throughout treatment for up to 2 years and through follow-up for up to 90 days

• Changes from baseline in weight

  Weight (kg or lb) and body surface area (m2) will be collected at Screening and on each dose day before any study treatment is administered and will be summarized by descriptive statistics at each visit, including change from baseline. Height (cm or in) will be recorded at baseline only

  From screening for up to 28 days, throughout treatment for up to 2 years and through follow-up for up to 90 days

• Occurrence of dose limiting toxicities (DLTs)

  All adverse events meeting the DLT criteria will be considered a DLT potentially related to the study treatment, regardless of Investigator/Sponsor causality assessment, excluding toxicities that are clearly related to disease progression or inter-current illness. DLTs will be considered by the safety monitoring committee for the purposes of dosing decisions.

  During phase 1 Part A: from the first dose of BI-1910 for 21 days. During phase 1 part B: from the first dose of BI-1910 for 42 days.

• identification of dose/dose range fulfilling favorable PK and pharmacodynamic profile, with acceptable safety

  based on the totality of the efficacy, safety, PK, and pharmacodynamic endpoints

  During phase 2a from screening for up to 28 days, throughout treatment for up to 2 years and through follow-up for up to 90 days

Secondary Outcomes (7)

• Maximum Concentration (Cmax) of BI-1910

  From the start of the study treatment for up to 2 years and 90 days.

• Serum concentration-time curve [AUC] of BI-1910

  From the start of the study treatment for up to 2 years and 90 days.

• Terminal half-life (t½) of BI-1910

  From the start of the study treatment for up to 2 years and 90 days.

• Recommended dose range (RDR)

  During phase 1 From screening for up to 28 days, throughout treatment for up to 2 years and through follow-up for up to 90 days

• Incidence and titer of antidrug antibodies (ADAs).

  From the start of the study treatment for up to 2 years and 90 days.

Study Arms (4)

Phase I, Part A - Dose escalation and safety of BI-1910 as single agent

EXPERIMENTAL

Dose escalation of BI-1910 administered as a single agent.

Drug: BI-1910

Phase I, Part B - Dose escalation and safety of BI-1910 in combination with pembrolizumab

EXPERIMENTAL

Dose escalation of BI-1910 in combination with pembrolizumab.

Drug: BI-1910; Drug: Pembrolizumab

Phase 2a, Part A - Dose expansion of BI-1910 as single agent

EXPERIMENTAL

BI-1910 administered as a single agent at the hypothesized recommended phase 2 dose determined in Phase 1.

Drug: BI-1910

Phase 2a, Part B - Dose expansion of BI-1910

EXPERIMENTAL

BI-1910 administered in combination with pembrolizumab at the respective hypothesized recommended phase 2 doses determined in Phase 1

Drug: BI-1910; Drug: Pembrolizumab

Interventions

BI-1910 DRUG

BI-1910 administered as a flat-dose IV infusion once every 3 weeks

Phase 2a, Part A - Dose expansion of BI-1910 as single agent; Phase 2a, Part B - Dose expansion of BI-1910; Phase I, Part A - Dose escalation and safety of BI-1910 as single agent; Phase I, Part B - Dose escalation and safety of BI-1910 in combination with pembrolizumab

Pembrolizumab DRUG

Pembrolizumab be administered as an IV infusion at its standard flat dose (200 mg) once every 3 weeks prior to the BI-1910 infusion

Phase 2a, Part B - Dose expansion of BI-1910; Phase I, Part B - Dose escalation and safety of BI-1910 in combination with pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Is willing and able to provide signed informed consent for the trial.
• Is ≥18 years of age on the day of signing the informed consent form.
• Has a histologically-confirmed advanced/metastatic solid tumor.
• Has received standard of care and progressed or is intolerant of, or is not eligible to receive standard of care antineoplastic therapy.
• Has at least 1 measurable disease lesion as defined by RECIST v1.1.
• Must be willing to provide tumor biopsies as specified in the schedule of assessments
• Has a life expectancy of ≥12 weeks.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate organ function as confirmed by laboratory values.

You may not qualify if:

• Needs doses of prednisolone \>10 mg daily (or equipotent doses of other corticosteroids) while on the trial other than as premedication.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has known or suspected hypersensitivity to BI-1910 or pembrolizumab.
• Has cardiac or renal amyloid light-chain amyloidosis.
• Has received the following:
• Chemotherapy or small molecule anti-cancer therapy products within 4 weeks, or 5 half-lives of the respective drug whichever is longer, of first dose of BI-1910.
• Radiotherapy within 2 weeks of first dose of BI-1910. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) for non-CNS disease.
• Subjects who have previously had radiation pneumonitis are not allowed.
• Immunotherapy within 4 weeks prior to the first dose of BI-1910.
• Has not recovered from AEs to at least Grade 1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v5.0 or higher).
• Has had Grade ≥3 autoimmune manifestations of previous immune checkpoint inhibitor treatments (e.g., anti-PD-1, anti-PD-L1, or anti-CTLA-4).
• Has a history of (noninfectious) 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). However, those female subjects who have a negative serum or urine pregnancy test up to 72 hours prior to their first dose of study treatment and agree to use a highly effective method of birth control for 4 weeks before entering the trial, during the trial, and for 12 months after their last dose of study treatment are considered eligible.
• Is a male subject with partner(s) of childbearing potential (unless he agrees to use a barrier method of contraception \[condom plus spermicidal gel\] with the female partner(s) who are using one highly effective method of contraception during the trial and for 12 months after completing treatment).

Sponsors & Collaborators

• BioInvent International AB: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (8)

Rigshospitalet

Copenhagen, Denmark

Location

Universitätsklinikum Essen

Essen, Germany

Location

Hospital HM Nou Delfos

Barcelona, 08023, Spain

Location

HM Sanchinarro

Madrid, Spain

Location

Hospital Fundacion Jimenez Diaz

Madrid, Spain

Location

Hospital universitario Virgen del Rocio

Seville, Spain

Location

Lund University Hospital

Lund, Sweden

Location

Karolinska University Hospital, Solna

Stockholm, Sweden

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Hepatocellular

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases

Study Officials

• Andres McAllister, PhD

  BioInvent International AB

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a Phase 1/2a, open-label, dose-escalation, multicenter, FIH, consecutive-cohort, clinical trial of BI-1910, as a single agent and in combination with pembrolizumab.

Study Record Dates

• First Submitted: December 18, 2023
• First Posted: January 16, 2024
• Study Start: December 4, 2023
• Primary Completion (Estimated): July 14, 2027
• Study Completion (Estimated): November 7, 2028
• Last Updated: September 19, 2025

Record last verified: 2025-09

Locations

SE (2); ES (4); DK (1); DE (1)