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

NCT04752826 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: 19-BI-1808-01MK3475-D202020-002090-10
• Study Type: interventional
• Target: 176
• Locations: 7 countries
• Sites: 25

Brief Summary

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),

Conditions

Advanced Malignancies; Ovarian Cancer; T-cell Lymphoma; Melanoma

Keywords

Advanced Malignancies; T-cell Lymphoma

Outcome Measures

Primary Outcomes (3)

• 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.

• 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)

  Select the RP2D dose for BI-1808ing mTPI-2 design.

  Up to 104 weeks (2 years)

• 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)

Secondary Outcomes (3)

• Evaluation of PK parameters for BI-1808. Maximum observed plasma concentration (Cmax)

  Up to 104 weeks (2 years)

• Evaluation of ADA response to BI-1808 in serum with validated method

  Up to 104 weeks (2 years)

• Measurement of TNFR2 receptor occupancy on CD14+ and/CD16+ cells in serum with validated method

  Up to 104 weeks (2 years)

Study Arms (4)

Phase I, Part A - Dose escalation and safety of BI-1808 as single agent

EXPERIMENTAL

Dose escalation of BI-1808 administrated a single agent

Drug: BI-1808

Phase I, Part B - Dose escalation and Safety of BI-1808 in combination with pembrolizumab

EXPERIMENTAL

Dose escalation of BI-1808 in combination with pembrolizumab.

Drug: BI-1808; Drug: Pembrolizumab (KEYTRUDA® ) 25 Mg/mL Solution for Injection

Phase 2a - Part A dose expansion of BI-1808 as a single agent

EXPERIMENTAL

BI-1808 administered as a single agent at the hypothesized recommended phase 2 dose determined in Phase 1

Drug: BI-1808

Phase 2a, Part B - Dose expansion of BI-1808 in combination with pembrolizumab

EXPERIMENTAL

BI-1808 administered in combination with pembrolizumab at the respective hypothesized recommended phase 2 doses determined in Phase 1

Drug: BI-1808; Drug: Pembrolizumab (KEYTRUDA® ) 25 Mg/mL Solution for Injection

Interventions

BI-1808 DRUG

BI-1808 administered as a flat-dose IV infusion once every 3 weeks

Phase 2a - Part A dose expansion of BI-1808 as a single agent; Phase 2a, Part B - Dose expansion of BI-1808 in combination with pembrolizumab; Phase I, Part A - Dose escalation and safety of BI-1808 as single agent; Phase I, Part B - Dose escalation and Safety of BI-1808 in combination with pembrolizumab

Pembrolizumab (KEYTRUDA® ) 25 Mg/mL Solution for Injection DRUG

Pembrolizumab administered as a flat-dose IV infusion once every 3 weeks.

Phase 2a, Part B - Dose expansion of BI-1808 in combination with pembrolizumab; Phase I, Part B - Dose escalation and Safety of BI-1808 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 written informed consent for the trial.
• Is ≥18 years of age on the day of signing informed consent.
• Has a histologically confirmed advanced malignancy. Subjects with CTCL \[MF or SS\] who satisfy the Phase 2a, Cohort 3-specific eligibility criteria may be enrolled into the Phase 1 part of the study.
• Is intolerant of, refuses, or is not eligible for standard antineoplastic therapy.
• Has at least 1 measurable disease lesion as defined by RECIST.
• Is able to safely undergo a baseline tumor tissue biopsy prior to first dose of BI-1808 (on non previously irradiated lesions only). The biopsy must be performed at least 4 weeks following the last dose of tumor directed therapy.
• Has a life expectancy of ≥12 weeks.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Has adequate organ function as confirmed by laboratory values.
• Ovarian Cancer:
• Histologically confirmed and documented recurrent ovarian, fallopian tube, and peritoneal cancer.
• TCL:
• histologically confirmed diagnosis
• Stable doses of systemic steroids (≤20 mg prednisone equivalent) and of low-to-medium potency topical steroids permitted (no change in preceding 4 weeks).
• Stage IB-IV with failure of at least 1 systemic therapy.

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-1808 or pembrolizumab
• Has cardiac or renal amyloid light-chain amyloidosis.
• Has received the following:
• Chemotherapy or small molecule products within 4 weeks of first dose of BI-1808.
• Radiotherapy within 2 weeks of first dose of BI-1808. 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-1808.
• Has not recovered from AEs to at least Grade 1 by NCI CTCAE
• Has had Grade ≥3 autoimmune manifestations of previous immune checkpoint inhibitor treatments (eg, 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 before enrollment 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 last dose of BI-1808, are considered eligible.
• Is a male subject with partner(s) of childbearing potential (unless he agrees to take measures not to father children by using 1 form of highly effective contraception \[condom plus spermicide gel\] during the trial and for 12 months after completing treatment).
• Has had major surgery from which the subject has not yet recovered.

Sponsors & Collaborators

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

Study Sites (25)

City of Hope National Medical Center

Duarte, California, 91010, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Rigshospitalet

Copenhagen, Denmark

RECRUITING

Herlev Hospital

Herlev, 2730, Denmark

RECRUITING

PRA Health Sciences - Hungary

Budapest, 1077, Hungary

ACTIVE NOT RECRUITING

Magyar Honvédség-Egészségügyi Központ

Budapest, 1134, Hungary

RECRUITING

Debreceni Egyetem Klinikai Központ

Debrecen, 4032, Hungary

WITHDRAWN

Byudzhetnoye Uchrezhdeniye Zdravookhraneniya Omskoy Oblasti - Klinicheskiy Onkologicheskiy Dispanser

Omsk, 644013, Russia

TERMINATED

National Medical Research Center VA Almazov

Saint Petersburg, 197022, Russia

WITHDRAWN

N.N. Petrov National Medical Research Center of Oncology

Saint Petersburg, 197758, Russia

WITHDRAWN

Institut Catala d'oncologia. Hospital Duran I Reynals

Barcelona, 08907, Spain

NOT YET RECRUITING

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

RECRUITING

START Madrid - Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

NOT YET RECRUITING

Sahlgrenska University Hospital

Gothenburg, 41345, Sweden

RECRUITING

Skanes University Hospital

Lund, 223 70, Sweden

RECRUITING

Karolinska University Hospital, Solna

Stockholm, 17176, Sweden

RECRUITING

University Hospital Birmingham

Birmingham, United Kingdom

RECRUITING

University Hospitals of Leicester NHS Trust

Leicester, LE1 5WW, United Kingdom

RECRUITING

Guy's and Saint Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

RECRUITING

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

RECRUITING

The Royal Marsden Hospital NHS Foundation Trust

London, United Kingdom

RECRUITING

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Ovarian Neoplasms; Lymphoma, T-Cell; Melanoma

Interventions

pembrolizumab; Solutions; Injections

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Andres McAllister, PhD

  BioInvent International AB

  STUDY DIRECTOR

Central Study Contacts

Susanne Gertsson

CONTACT

+46462868550; susanne.gertsson@bioinvent.com

Mona Welschof, PhD

CONTACT

+47 97088721; mona.welschof@bioinvent.com

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: Phase 1/2a, dose escalation, consecutive-cohort, open-label study trial of BI-1808 as a Single Agent and in Combination with Pembrolizumab in Subjects with advanced malignancies.

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: February 12, 2021
• Study Start: January 25, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): January 15, 2028
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

SE (3); GB (7); US (3); HU (3); RU (3); DK (2); ES (4)