BI-1808 Combo Improves Efficacy vs Pembrolizumab Alone in Ovarian Cancer

The addition of BI-1808 to pembrolizumab (Keytruda) exhibited improved efficacy and a greater response rate compared with pembrolizumab alone as a treatment for patients with recurrent ovarian cancer, including high-grade serous and clear cell subtypes, who experienced progression following the receipt of platinum-based chemotherapy in a phase 1/2a trial (NCT04752826), according to a news release from the developer, BioInvent International.¹

Interim data from the phase 1/2a trial revealed that among patients with recurrent ovarian cancer, the overall response rate (ORR) was 24% vs 8% with pembrolizumab alone in the phase 2 KEYNOTE-100 trial (NCT02674061).² Moreover, some responses with the BI-1808 combination were observed following several months of treatment, which suggest that additional responses could be observed. The disease control rate (DCR) was 65%, with 4 patients experiencing partial responses and 7 experiencing stable disease.

Furthermore, the combination was well-tolerated, and adverse effects (AEs) were managed with standard medical treatments. Exploratory analyses showed strong activity in high-grade and clear cell histologies. The developers plan to expand the phase 2a trial to enroll 20 additional patients with these subtypes to be read out in the second half of 2026.

"Recurrent ovarian cancer has few options after platinum failure and a history of unsuccessful attempts to develop chemotherapy-free immunotherapy approaches," Martin Welschof, chief executive officer of BioInvent, stated in the news release.¹ "Pembrolizumab has shown meaningful benefit only when combined with chemotherapy, while monotherapy in the KEYNOTE-100 study achieved an ORR of 8%. Against this backdrop, observing [an ORR of] 24% and a [DCR of] 65% with BI-1808 in combination with pembrolizumab is highly encouraging and has led us to expand this cohort to better qualify this signal. These results suggest that our combination could deliver a new immuno-oncology option for patients who urgently need better alternatives, and we look forward to reporting more data going forward."

Investigators assigned 23 patients with recurrent ovarian cancer to receive the BI-1808 combination. In part A of the study, patients received BI-1808 as a single agent, and in part B, in combination with pembrolizumab at the recommended phase 2 dose found in phase 1.

The primary end points of the phase 1 trial included the incidence of any-grade and serious AEs and dose-limiting toxicities (DLTs). Secondary end points included pharmacokinetic and pharmacodynamic parameters for BI-1808, anti-drug antibody response, ORR, duration of response, and progression-free survival per RECIST v 1.1 criteria.³

The developers engineered BI-1808 as an anti-TNFR2 antibody as a part of their tumor-associated regulatory T cells (Treg)–targeting program. TNFR2 was shown to be important for tumor expansion and survival, with the marker displaying upregulation on Tregs.

Eligibility criteria for patients 18 years and older included a histological confirmation of an advanced malignancy, no prior receipt of standard antineoplastic surgery, at least 1 measurable disease lesion defined by RECIST v1.1 criteria, and ability to safely undergo baseline tumor biopsy at least 4 weeks following last dose of tumor-directed therapy. Additional eligibility criteria included a life expectancy of at least 12 weeks, an ECOG performance status score of 0 to 1, and adequate organ function as confirmed by laboratory values.

Patients were ineligible for trial inclusion if they had receipt of daily prednisolone dosing at 10 mg or greater, active central nervous system metastases and/or carcinomatous meningitis, or a known or suspected hypersensitivity to BI-1808 or pembrolizumab. Those who received prior chemotherapy, small molecule products, or immunotherapy within 4 weeks of the initial dose of BI-1808, or prior radiotherapy within 2 weeks of BI-1808 dosing, were also unable to enroll on the trial.

References

1. BioInvent reports promising data from ongoing phase 2a study for BI-1808 with KEYTRUDA(R) (pembrolizumab) in recurrent ovarian cancer. News release. BioInvent International. January 5, 2026. Accessed January 5, 2026. https://tinyurl.com/3mvpnvvd
2. Matulonis UA, Shapira R, Santin A, et al. Final results from the KEYNOTE-100 trial of pembrolizumab in patients with advanced recurrent ovarian cancer. J Clin Oncol. 2020;38(suppl 15):6005. doi: 10.1200/JCO.2020.38.15_suppl.6005
3. BI-1808 as a single agent and with pembrolizumab (KEYTRUDA® ) in treatment of advanced malignancies(Keynote-D20). ClinicalTrials.gov. Updated February 6, 2025. Accessed January 5, 2026. https://tinyurl.com/746ruedy