FDA Grants Fast Track Designation to Next-Generation ADC Based on Phase I/II Trial Data

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The FDA has granted Fast Track designation to an application from BioNTech SE and Duality Biologics Co., for BNT325/DB-1305, a next-generation antibody-drug conjugate (ADC) for patients with platinum-resistant ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer previously administered one to three systemic treatment regimens.¹ BNT325/DB-1305 targets trophoblast cell-surface antigen 2 (TROP2), a protein that is overexpressed across various tumor types.

“The FDA’s decision is an important recognition of the potential of our TROP2-targeting ADC candidate. Platinum-based chemotherapy is the backbone of treatment for ovarian epithelial cancer and related subtypes that form in the epithelial tissue,” Özlem Türeci, MD, BioNTech chief medical officer and co-founder, said in a press release. “Patients with platinum resistance who relapse within under six months have a poor prognosis, and effective and well-tolerated treatment options remain a substantial unmet medical need. Recent studies have indicated the role of TROP2 in aggressive tumor growth and progression in patients with chemotherapy-resistant ovarian tumors. We are committed to further advancing BNT325/DB-1305 and believe that a TROP2-targeted treatment approach has the potential to overcome current limitations in the treatment of advanced ovarian cancers.”¹

The regulatory action was based on preliminary findings from the ongoing, global, open-label, first-in-human Phase I/II NCT05438329 trial. The study evaluated patients with advanced or metastatic solid tumors who either progressed on standard therapy or who do not have standard therapy available.²

The trial’s first phase analyzed five escalating doses of the ADC at 2 mg/kg, 4 mg/kg, 6 mg/kg, 8 mg/kg, and 10 mg/kg to determine the recommended dose for the second phase.

The second phase analyzed the safety and efficacy of the novel therapy in patients with small cell lung cancer; HR-positive and HER2-negative breast cancer; oncogene driven–negative non–small cell lung cancer (NSCLC); Trodelvy (sacituzumab govitecan-hziy)–naive patients with triple-negative breast cancer (TNBC); Trodelvy–exposed patients with TNBC; NSCLC with actionable genomic alterations; and other solid tumors, which favored referral for patients with epithelial ovarian and endometrial cancer.

The trial’s primary endpoints included safety, with secondary endpoints that included objective response rate (ORR), disease control rate (DCR), duration of response, time to response, progression-free survival, and overall survival.

The data show BNT325/DB-1305 produced an ORR of 30.4% with an unconfirmed DCR of 87.0% among individuals with TROP-expressing advanced solid tumors previously administered a median of three lines of therapy. One patient in the trial with fallopian tube cancer achieved an unconfirmed partial response at the 5 mg/kg dose.

Treatment-related adverse effects occurring in at least 20% of patients were stomatitis (all grade, 75.0%; grade ≥3, 22.7%), nausea (29.5%; 2.3%), decreased lymphocyte count (22.7%; 13.6%), infusion-related reaction (20.5%; 0%), decreased appetite (20.5%; 0%), mucosal inflammation (0%; 2.3%), and interstitial lung disease (2.3%; 0%).²

“BNT325/DB-1305 is the second investigational asset in our strategic collaboration which has received FDA Fast Track designation highlighting the potential of the candidate to fill an unmet medical need,” said Vivian Gu, MD, DualityBio chief medical officer, in a press release. “Data from the Phase I/II clinical trial with BNT325/DB-1305 have demonstrated encouraging anti-tumor signals in heavily pretreated patients with TROP2-expressing solid tumors who had failed standard therapy with an objective response rate of 30.4% and a disease control rate of 87.0%. We look forward to progressing the further development of BNT325/DB-1305 within the fast track framework, and hope to be one step closer to potentially improving outcomes for a range of patients.”¹

References

1. BioNTech and DualityBio receive FDA fast track designation for next-generation antibody-drug conjugate candidate BNT325/DB-1305. News release. BioNTech SE. January 31, 2024. Accessed February 6, 2024. https://investors.biontech.de/news-releases/news-release-details/biontech-and-dualitybio-receive-fda-fast-track-designation-next

2. Marathe O, Cheng Y, Spira AI, et al. DB-1305 (a Trop-2 targeted antibody-drug-conjugate [ADC]) in patients (pts) with advanced solid tumors: Preliminary clinical results from the phase (Ph) I/IIa study. Ann Oncol. 2023;34(suppl 2):S480. doi:10.1016/j.annonc.2023.09.1875. Accessed February 6, 2024.