The anti-TNFR2 antibody BI-1808 is part of BioInvent’s tumor-associated regulatory T cells (Treg)-targeting program. TNFR2 is particularly upregulated on Tregs of the tumor microenvironment and has been shown to be important for tumor expansion and survival, representing a new and promising target for cancer immunotherapy.
BI-1808 could represent a new class of immunomodulatory agent with the potential to improve efficacy of cancer therapy
In March 2025, the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation (ODD) for BI-1808 for the treatment of T-cell Lymphoma (TCL).
T-cell lymphomas include a number of subtypes of T cell-derived non-Hodgkins’s lymphoma, including cutaneous T-cell lymphoma (CTCL). CTCL is a rare and aggressive form that originates in T-lymphocytes residing in the skin. It typically manifests with persistent skin lesions, itching, and potential systemic complications, significantly impacting patients’ quality of life. Each year, approximately 3,000 new cases are diagnosed in the United States with limited effective treatment options available.
In September 2024, additional positive data from the ongoing study with BI-1808 as monotherapy was announced:
- Three partial responses (PR) and one stable disease (SD) out of four evaluable patients with Cutaneous T-cell Lymphoma (CTCL) observed in the single agent part of the Phase 2a study. Three other patients in the cohort were considered non-evaluable
- All patients had progressed after standard therapy. The three responding patients had received 9, 3 and 3 previous lines of treatment respectively, and one of them included previous anti-PD1 treatment.
- The CTCL data support earlier data showing one complete response (CR), one PR and nine patients with stable disease (SD) presented at the American Society of Clinical Oncology conference in June 2024.
- BI-1808 continues to be impressively safe and well tolerated.
Pembrolizumab combination safety and efficacy data presented at ASCO in June 2024
- Safety: BI-1808 in combination with pembrolizumab is well tolerated. With 19 patients dosed, two DLTs (Dose-limiting toxicities) have been observed (1 colitis and 1 fatigue).
- Efficacy: 3 of 8 evaluable patients showed SD after combination treatment.
- Pharmacology: At doses of 675 mg every three weeks, the half-life of BI-1808 was approximately one week leading to drug accumulation, complete receptor occupancy during the treatment interval, an increase in soluble TNFR2 and a significant reduction in Tregs.
BI-1808 is evaluated both as a single agent and in combination with pembrolizumab in subjects with advanced malignancies, whose disease has progressed after standard therapy.
Study design
BI-1808 is being studied as both a single agent and in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in patients with advanced solid tumors or T-cell lymphomas, including CTCL. The Phase 2a single agent as well as combination part are in the dose expansion phase testing the activity in four different groups: ovarian cancer (OC), melanoma, all tumor types and TCL/CTCL.
Read more about the ongoing Phase 1/2a study KEYNOTE-D20
Evaluation of BI-1808 for the treatment of solid tumors and T-cell lymphomas.
Out-licensing and partnering
In August 2021, BioInvent entered into a second clinical trial collaboration and supply agreement with Merck. This time to evaluate the combination of BioInvent’s BI-1808 and Merck’s anti-PD-1 therapy, Keytruda in a Phase 1/2a clinical trial in patients with advanced solid tumors. Under the agreement, Merck supplies Keytruda which supports the evaluation of BI-1808 in combination with one of the most successful immuno-oncology drugs on the market.