The FDA has granted quick monitor designation to the antibody-drug conjugate (ADC) BNT324/DB-1311 as a possible therapy choice for sufferers with unresectable superior or metastatic castration-resistant prostate most cancers (mCRPC) who’ve progressed on or after customary systemic regimens.1
The following-generation ADC is designed to focus on the transmembrane glycoprotein B7-H3, which is an immune checkpoint protein overexpressed in quite a lot of stable tumors and is related to illness development and poor prognosis. An ongoing section 1/2 trial (NCT05914116) is evaluating BNT324/DB-1311 in sufferers with superior stable tumors.
“The FDA’s resolution is a recognition of the potential of our B7-H3–focusing on ADC candidate for the therapy of [patients with] superior CRPC. [Although] sufferers with metastatic prostate most cancers initially reply to hormone remedy, most sufferers progress after 18 to 24 months and develop CRPC, a complicated type of prostate most cancers, resulting in a poor prognosis for these sufferers. The 5-year survival price for sufferers with mCRPC is just round 36%,” Özlem Türeci, MD, chief medical officer and co-founder of BioNTech, acknowledged in a information launch. “We’re dedicated to additional advancing BNT324/DB-1311 with our accomplice DualityBio and imagine {that a} focused ADC immunotherapy strategy has the potential to enhance outcomes for sufferers at superior phases of the illness.”
Together with focusing on B7-H3, BNT324/DB-1311 contains a topoisomerase I inhibitor payload. Preclinical research confirmed that the ADC produced antitumor exercise in quite a lot of stable tumor fashions, and preliminary knowledge from the section 1/2 trial have proven efficacy with manageable toxicity.
The primary-in-human, multicenter, open-label dose-escalation and -expansion research is enrolling sufferers not less than 18 years of age with histologically or cytologically confirmed, unresectable superior or metastatic stable tumors which have relapsed or progressed on or after customary systemic remedies; are insupportable to plain therapy; or haven’t any customary therapy obtainable.2
Key inclusion standards for all sufferers embody not less than 1 measurable lesion per RECIST v1.1 standards; a life expectancy of not less than 3 months; an ECOG efficiency standing of 0 or 1; and a left ventricular ejection fraction of not less than 50%.
Sufferers with CRPC being enrolled into cohort 4 of section 2a are required to have pathologically documented metastatic adenocarcinoma of the prostate, the place progressive mCRPC is outlined as castrate ranges of serum testosterone lower than 50 ng/dL and progressive illness per Prostate Most cancers Working Group 3 standards. Prior docetaxel, both earlier than or after androgen receptor–focused remedy, is required, and docetaxel rechallenge can also be permitted. Prior novel hormone remedy can also be wanted for enrollment.
Prior therapy with B7-H3–focused remedy will exclude sufferers from participation, and those that obtained prior therapy with an ADC containing a topoisomerase I inhibitor is not going to be included. Different key exclusion standards embody a medical historical past of symptomatic congestive coronary heart failure or severe cardiac arrhythmia requiring therapy; a medical historical past of myocardial infarction or unstable angina inside 6 months earlier than enrollment; or a mean QTcF prolongation to larger than 470 ms.
Throughout dose escalation, BNT324/DB-1311 is being administered at 1 of 5 dose ranges on day 1 of every 3-week cycle. Dose enlargement will characteristic tumor-specific cohorts, together with mCRPC, small cell lung most cancers, non–small cell lung most cancers, esophageal squamous cell carcinoma, melanoma, and different tumors.
In section 1, the first finish factors are figuring out the proportion of sufferers with dose-limiting toxicities; figuring out the proportion of sufferers with treatment-emergent adversarial results (TEAEs) and severe AEs; and figuring out the utmost tolerated dose and really helpful section 2 dose. Part 2’s major finish factors encompass the speed of TEAEs and severe AEs; and goal response price per RECIST v1.1 standards. Pharmacokinetics are a secondary finish level.
References
- BioNTech and DualityBio obtain FDA quick monitor designation for antibody-drug conjugate candidate BNT324/DB-1311 in prostate most cancers. Information launch. BioNTech. June 24, 2024. Accessed July 8, 2024. https://traders.biontech.de/news-releases/news-release-details/biontech-and-dualitybio-receive-fda-fast-track-designation
- A research of DB-1311 in superior/metastatic stable tumors. ClinicalTrials.gov. Up to date September 13, 2023. Accessed July 8, 2024. https://clinicaltrials.gov/research/NCT05914116
