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FDA Grants Fast Track Designation to BI-1808 in Select Cutaneous T-Cell Lymphoma

BI-1808 has received FDA fast track designation for the treatment of patients with select cutaneous T-cell lymphoma subtypes.

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The FDA has granted breakthrough therapy designation to the first-in-class anti–tumor necrosis factor receptor 2 (TNFR2) antibody, BI-1808 for the treatment of adults with 2 cutaneous T-cell lymphoma (CTCL) subtypes: relapsed or refractory mycosis fungoides and Sézary syndrome.1

"Receiving the FDA's fast track designation following the recent orphan drug designation underscores the potential of this novel immunomodulatory agent and reflects the urgent need for new, safe, and durable treatment options for patients with CTCL", Martin Welschof, CEO of BioInvent, stated in a news release. "It's very encouraging that the FDA confirms that the presented BI-1808 data meet expectations to address this important unmet medical need". To date, BI-1808 demonstrated early clinical efficacy in heavily pretreated patients with an excellent safety and tolerability profile. We are committed to continue advancing the development of BI-1808 and look forward to providing an update from the ongoing phase 2a [study] by mid-2025."

Targeting TNFR2 represents a novel therapeutic strategy with the potential to enhance antitumor activity, particularly when combined with PD-1 inhibitors such as pembrolizumab.2 BI-1808, a TNFR2-targeted antibody, has demonstrated significant depletion of regulatory T cells and robust CD8-positive T-cell activation in responding patients, suggesting immune reprogramming within the tumor microenvironment. Notably, BI-1808 has exhibited single-agent activity in tumor types that have historically shown limited responsiveness to immune checkpoint blockade, further supporting its potential as a complementary immunotherapy.

The safety, tolerability, and early efficacy of BI-1808 as monotherapy (part A) and in combination with pembrolizumab (Keytruda; part B) are under investigation in the phase 1/2a 19-BI-1808-01 study (NCT04752826) in patients with advanced solid tumors and T-cell lymphoma.1 Early data from the ongoing phase 2a dose expansion cohort, presented at the 2024 ASCO Annual Meeting, showed that single-agent BI-1808 induced 1 complete response (CR), 1 partial response (PR), and 9 cases of stable disease (SD) among 26 evaluable patients with cutaneous T-cell lymphoma (CTCL).2,3

Additional preliminary efficacy data reported in September 2024 demonstrated 3 PRs and 1 SD among 4 evaluable patients with CTCL who received BI-1808 monotherapy, all of whom remain on treatment.3 Three other patients were considered non-evaluable. All treated patients had progressed following standard therapies, including one who previously received an anti–PD-1 agent.

"Receiving the FDA's fast track designation following the recent orphan drug designation underscores the potential of this novel immunomodulatory agent and reflects the urgent need for new, safe, and durable treatment options for patients with CTCL,” Martin Welschof, CEO of BioInvent, stated in a news release.1 "It's very encouraging that the FDA confirms that the presented BI-1808 data meet expectations to address this important unmet medical need". To date, BI-1808 demonstrated early clinical efficacy in heavily pretreated patients with an excellent safety and tolerability profile. We are committed to continue advancing the development of BI-1808 and look forward to providing an update from the ongoing phase 2a [study] by mid-2025."

Phase 1/2 Study Overview

Patients must be at least 18 years of age, have a histologically confirmed advanced malignancy, be intolerant of, refuse, or be ineligible for standard antineoplastic therapy, have at least 1 measurable disease lesion as defined by RECIST 1.1 criteria, have an ECOG performance status of 0 or 1.4

In the phase 1 dose escalation, single-agent BI-1808 will be administered at ascending doses of 25 mg, 75 mg, 225 mg, 675 mg, and 1000 mg.2 In the dose-escalation portion, patients will receive either the 225 mg, 675 mg, or 1000 mg dose of BI-1808 alongside 200 mg of pembrolizumab every 3 weeks according to an mTPI-2 design.

The study’s primary end points include safety, dose-limiting toxicities, and determining the maximum tolerated dose and selecting a recommended phase 2 dose.4 Secondary end points include assessments of the agent’s pharmacokinetics and pharmacodynamic profile.

The ongoing phase 2a portion of the trial is evaluating BI-1808 as monotherapy in larger expansion cohorts that include patients with ovarian cancer, melanoma, T-cell lymphomas, and other solid tumors; and BI-1808 in combination with pembrolizumab for patients with non–small cell lung cancer, ovarian cancer, T-cell lymphomas, and melanoma.1,2 Dose escalation in phase 1 part B has been completed, and the phase 2a dose expansion is ongoing.1 Additional single-agent data are anticipated in mid-2025.

References

  1. BioInvent receives FDA fast track designation for BI-1808 for the treatment of cutaneous T-cell lymphoma. News Release. BioInvent. April 29, 2025. Accessed May 2, 2025. https://www.bioinvent.com/en/press/bioinvent-receives-fda-fast-track-designation-bi-1808-treatment-cutaneous-t-cell-lymphoma
  2. Rohrberg KS, Papai Z, Eefsen RL, et al. 19-BI-1808-01, a phase 1/2a clinical trial of BI-1808, a tumor necrosis factor receptor 2 (TNFR2) blocker/depleter with or without pembrolizumab. J Clin Oncol. 2024;42(suppl 16):2641. doi:10.1200/JCO.2024.42.16_suppl.2641
  3. BioInvent announces additional positive efficacy ata with single agent BI-1808 from the phase 2a anti-TNFR2 program. News Release. BioInvent. September 9, 2024. Accessed May 2, 2025. https://www.bioinvent.com/en/press/bioinvent-announces-additional-positive-efficacy-data-single-agent-bi-1808-phase-2a-anti
  4. BI-1808 as a single agent and with pembrolizumab (KEYTRUDA® ) in the treatment of advanced malignancies (Keynote-D20). ClinicalTrials.gov. Updated February 6, 2025. Accessed May 2, 2025. https://clinicaltrials.gov/study/NCT04752826

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