BI-1808 as a Single Agent and With Pembrolizumab (KEYTRUDA® ) in Treatment of Advanced Malignancies(Keynote-D20)

Phase 1/2a Open-Label, Dose-Escalation, Multicenter, FIH, Consecutive-Cohort, Clinical Trial of BI-1808, a Monoclonal Antibody to TNFR 2 as a Single Agent and in Combination With Pembrolizumab (MK-3475-D20) in Subjects With Advanced Malignancies

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 with BI-1808 as a single agent, BI-1808 in combination with pembrolizumab and BI-1808 in combination with pembrolizumab and paclitaxel 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),

Study Overview

• Status: Recruiting
• Conditions: Melanoma; Ovarian Cancer; Advanced Malignancies; T-cell Lymphoma
• Intervention / Treatment: Drug: BI-1808; Drug: Pembrolizumab (KEYTRUDA® ) 25 Mg/mL Solution for Injection; Drug: Paclitaxel 80 mg/m2 weekly

Detailed Description

This is a Phase 1/2a, dose-escalation, multicenter, first-in-human, consecutive-cohort, open-label study of BI-1808, as a single agent, in combination with pembrolizumab, and in BI-1808 in combination with pembrolizumab and paclitaxel in subjects with advanced malignancies, whose disease has progressed after standard therapy.

The study will consist of 2 phases: a Phase 1 with Parts A and B, and a Phase 2a with Parts A , B and C.

Phase 1 Part A consists of a dose escalation of BI-1808 as a single agent to evaluate safety and tolerability and to determine the RP2D as a single agent (sRP2D) in subjects with advanced malignancies whose disease has progressed after standard therapy.

Phase 1 Part B consists of a dose escalation of BI-1808 in combination with pembrolizumab to evaluate the safety and tolerability of the combination treatment and to allow selection of the RP2D for BI-1808 in combination with pembrolizumab (cRP2D) in subjects with advanced malignancies whose disease has progressed after standard therapy.

Phase 2a will assess BI-1808 administered as a single agent (Part A), in combination with pembrolizumab (Part B), and in combination with pembrolizumab and paclitaxel (Part C) at the respective hypothesized RP2D(s) determined in Phase 1. Phase 2a expansion will be conducted in indication specific signal seeking cohorts and indication specific Dose Optimization Cohorts) of subjects. The Phase 2a study aims to further evaluate the safety and tolerability of BI-1808 as monotherapy (Part A), in combination with pembrolizumab (Part B), and in combination with pembrolizumab and paclitaxel (Part C). Including characterization of the PK and PD profiles of BI-1808, evaluation of preliminary antitumor activity based on ORR, DoR, and progression-free survival (PFS) as assessed by RECIST v1.1 and iRECIST, and determination of the recommended Phase 2 dose (RP2D).

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Susanne Gertsson; Phone Number: +46462868550; Email: susanne.gertsson@bioinvent.com
• Study Contact Backup: Name: Mona Welschof, PhD; Phone Number: +47 97088721; Email: mona.welschof@bioinvent.com

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Rigshospitalet
    • Principal Investigator: Kristoffer Staal Rohrberg
  • Herlev, Denmark, 2730
    • Recruiting
    • Herlev Hospital
    • Principal Investigator: Rikke Løvendahl Eefsen
• Hungary
  • Budapest, Hungary, 1134
    • Recruiting
    • Magyar Honvédség-Egészségügyi Központ
    • Principal Investigator: Zsuzsanna Pápai
  • Budapest, Hungary, 1077
    • Active, not recruiting
    • PRA Health Sciences - Hungary
  • Debrecen, Hungary, 4032
    • Withdrawn
    • Debreceni Egyetem Klinikai Kozpont
• Russia
  • Omsk, Russia, 644013
    • Terminated
    • Byudzhetnoye Uchrezhdeniye Zdravookhraneniya Omskoy Oblasti - Klinicheskiy Onkologicheskiy Dispanser
  • Saint Petersburg, Russia, 197022
    • Withdrawn
    • National Medical Research Center VA Almazov
  • Saint Petersburg, Russia, 197758
    • Withdrawn
    • N.N. Petrov National Medical Research Center of Oncology
• Spain
  • Barcelona, Spain, 08907
    • Not yet recruiting
    • Institut Catala d'oncologia. Hospital Duran I Reynals
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Recruiting
    • START Madrid - Hospital Universitario Fundación Jiménez Díaz
  • Madrid, Spain, 28007
    • Not yet recruiting
    • Hospital Universitario Puerta de Hierro-Majadahonda, Madrid,
• Sweden
  • Gothenburg, Sweden, 41345
    • Recruiting
    • Sahlgrenska University Hospital
    • Principal Investigator: Edvard Abel
  • Lund, Sweden, 223 70
    • Recruiting
    • Skanes University Hospital
    • Principal Investigator: Ana Carnerio
  • Stockholm, Sweden, 17176
    • Recruiting
    • Karolinska University Hospital, Solna
    • Principal Investigator: Jeffrey Yachnin
• United Kingdom
  • Birmingham, United Kingdom
    • Recruiting
    • University Hospital Birmingham
    • Contact: Julia Scarisbrick, Prof.
  • Leicester, United Kingdom, LE1 5WW
    • Recruiting
    • University Hospitals of Leicester NHS Trust
    • Principal Investigator: Harriet Walter
  • London, United Kingdom, W1G 6AD
    • Recruiting
    • Sarah Cannon Research Institute UK
    • Principal Investigator: Anja Williams
  • London, United Kingdom, SE1 9RT
    • Recruiting
    • Guy's and Saint Thomas' NHS Foundation Trust
    • Principal Investigator: Stephen Morris
  • London, United Kingdom
    • Recruiting
    • The Royal Marsden Hospital NHS Foundation Trust
    • Principal Investigator: Juanita Lopez
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
    • Principal Investigator: Richard Cowan
  • Southampton, United Kingdom, SO16 6YD
    • Recruiting
    • Southampton General Hospital
    • Principal Investigator: Sean Lim
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center
      • Principal Investigator: Christiane Querfeld
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Jasmine Zain
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Principal Investigator: Stefan Barta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Able and willing to provide written informed consent.
• Aged 18 years or older.
• Histologically confirmed advanced or metastatic malignancy eligible for an enrolling study cohort.
• Disease progression following, intolerance of, ineligibility for, or refusal of applicable standard therapy.
• At least one measurable lesion according to the response criteria specified in the protocol.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Life expectancy of at least 12 weeks.
• Adequate organ function.
• Willing and medically suitable to provide required tumor or skin biopsies.
• Meets the disease-specific and treatment-history requirements of the applicable Phase 2a cohort.
• For Phase 2a Part C: Histologically confirmed platinum-resistant high-grade serous or clear-cell ovarian carcinoma, prior platinum-based treatment as specified in the protocol, and suitability for paclitaxel treatment.

Exclusion Criteria:

1. Active central nervous system metastases or carcinomatous meningitis.

• Active or clinically significant autoimmune disease, immunodeficiency, or use of prohibited immunosuppressive treatment.
• Prior treatment-related toxicity not recovered to the level specified in the protocol.
• Prior anticancer therapy, radiotherapy, immunotherapy, investigational treatment, or live vaccine within the protocol-defined washout period.
• History of clinically significant immune-mediated toxicity, including pneumonitis, associated with previous immune-checkpoint inhibitor treatment.
• Uncontrolled or clinically significant cardiovascular disease, serious infection, or another condition that could compromise safety or study participation.
• Major surgery without adequate recovery.
• Prior allogeneic tissue or solid-organ transplantation or active graft-versus-host disease.
• Pregnancy or breastfeeding, or unwillingness to comply with protocol-defined contraceptive requirements.
• Known hypersensitivity to a study treatment or its components.
• Another active malignancy, except for protocol-defined permitted malignancies.
• Participation in another interventional clinical trial that conflicts with this study.
• Unable or unlikely to comply with study procedures and requirements.
• For Phase 2a Part C: Receipt of prohibited colony-stimulating factors within the protocol-defined period before treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I, Part A - Dose escalation and safety of BI-1808 as single agent; Dose escalation of BI-1808 administrated a single agent	Drug: BI-1808; BI-1808 administered as a flat-dose IV infusion once every 3 weeks
Experimental: Phase I, Part B - Dose escalation and Safety of BI-1808 in combination with pembrolizumab; Dose escalation of BI-1808 in combination with pembrolizumab.	Drug: BI-1808; BI-1808 administered as a flat-dose IV infusion once every 3 weeks; Drug: Pembrolizumab (KEYTRUDA® ) 25 Mg/mL Solution for Injection; Pembrolizumab administered as a flat-dose IV infusion once every 3 weeks.
Experimental: Phase 2a - Part A dose expansion of BI-1808 as a single agent; BI-1808 administered as a single agent at the hypothesized recommended phase 2 dose determined in Phase 1	Drug: BI-1808; BI-1808 administered as a flat-dose IV infusion once every 3 weeks
Experimental: Phase 2a, Part B - Dose expansion of BI-1808 in combination with pembrolizumab; BI-1808 administered in combination with pembrolizumab at the respective hypothesized recommended phase 2 doses determined in Phase 1	Drug: BI-1808; BI-1808 administered as a flat-dose IV infusion once every 3 weeks; Drug: Pembrolizumab (KEYTRUDA® ) 25 Mg/mL Solution for Injection; Pembrolizumab administered as a flat-dose IV infusion once every 3 weeks.
Experimental: Phase 2a, Part C - Dose expansion of BI-1808 in combination with pembrolizumab and paclitaxel; BI-1808 administered in combination with pembrolizumab and paclitaxel at the respective hypothesized recommended phase 2 doses determined in Phase 1.	Drug: BI-1808; BI-1808 administered as a flat-dose IV infusion once every 3 weeks; Drug: Pembrolizumab (KEYTRUDA® ) 25 Mg/mL Solution for Injection; Pembrolizumab administered as a flat-dose IV infusion once every 3 weeks.; Drug: Paclitaxel 80 mg/m2 weekly; Paclitaxel administered as a flat-dose IV infusion weekly.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Up to 104 weeks (2 years)
Identify DLTs, determine the maximum tolerated dose and select a recommended Phase 2 dose (RP2D) of BI-1808, given via intravenous (IV) infusion, as a single agent (Phase 1, Part A), and in combination with pembrolizumab (Phase 1, Part B)	Determine the hypothesized RP2D dose for BI-1808 Phase 2a according to mTPI-2 design	Up to 104 weeks (2 years)
To identify the recommended Phase 2 dose (RP2D) of BI-1808,	Select the RP2D dose for BI-1808 derived from the totality of PK, PD, clinical response, safety,and tolerability observed in signal seeking and dose optimization cohorts.	up to 104 weeks (2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of PK parameters for BI-1808. Maximum observed plasma concentration (Cmax)	Study the PK profile of BI-1808 according to a non-compartmental analysis using a validated software	Up to 104 weeks (2 years)
Evaluation of ADA response to BI-1808 in serum with validated method	The detection and characterization of antibodies to BI-1808 will be performed using a validated method and will be evaluated for BI-1808 serum concentration to enable interpretation of the antibody data	Up to 104 weeks (2 years)
Measurement of TNFR2 receptor occupancy on CD14+ and/CD16+ cells in serum with validated method	evaluate the receptor occupancy of BI-1808 as a single agent and in combination with pembrolizumab or pembrolizumab and paclitaxel on T-cells expressing TNFR2 in absolute value	Up to 104 weeks (2 years)

Collaborators and Investigators

• Sponsor: BioInvent International AB
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Andres McAllister, PhD, BioInvent International AB

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2021
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 15, 2020
• First Submitted That Met QC Criteria: February 11, 2021
• First Posted (Actual): February 12, 2021

Study Record Updates

• Last Update Posted (Actual): September 18, 2026
• Last Update Submitted That Met QC Criteria: September 15, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Advanced Malignancies; T-cell Lymphoma
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Immune System Diseases; Neoplasms by Histologic Type; Genital Diseases, Female; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Lymphoma; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Hemic and Lymphatic Diseases; Ovarian Neoplasms; Melanoma; Lymphoma, T-Cell; Organic Chemicals; Pharmaceutical Preparations; Therapeutics; Drug Administration Routes; Drug Therapy; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Paclitaxel; Injections; pembrolizumab; Solutions
• Other Study ID Numbers: 19-BI-1808-01; 2023 (U.S. NIH Grant/Contract: GRAMMY Museum Foundation); MK3475-D20 (Other Identifier: Merck Sharp & Dohme Corp); 2023-509847-29-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No