BNT324/DB-1311 Receives Quick Monitor Designation From FDA for mCRPC
Quick monitor designation has been granted by the FDA to the antibody-drug conjugate (ADC) BNT324/DB-1311 to probably deal with sufferers with unresectable superior or metastatic castration-resistant prostate most cancers (mCRPC) whose illness had progressed on or after commonplace systemic regimens.1
The subsequent-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 choice is a recognition of the potential of our B7-H3–focusing on ADC candidate for the remedy 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 sophisticated type of prostate most cancers, resulting in a poor prognosis for these sufferers. The 5-year survival charge for sufferers with mCRPC is simply round 36%,” Özlem Türeci, MD, chief medical officer and co-founder of BioNTech, said 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 incorporates a topoisomerase I inhibitor payload. Preclinical research confirmed that the ADC produced antitumor exercise in quite a lot of stable tumor fashions, and preliminary information 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 at the very least 18 years of age with histologically or cytologically confirmed, unresectable superior or metastatic stable tumors which have relapsed or progressed on or after commonplace systemic remedies; are insupportable to plain remedy; or haven’t any commonplace remedy obtainable.2
Key inclusion standards for all sufferers embody at the very least 1 measurable lesion per RECIST v1.1 standards; a life expectancy of at the very least 3 months; an ECOG efficiency standing of 0 or 1; and a left ventricular ejection fraction of at the very least 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 be permitted. Prior novel hormone remedy can be wanted for enrollment.
Prior remedy with B7-H3–focused remedy will exclude sufferers from participation, and those that acquired prior remedy 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 critical cardiac arrhythmia requiring remedy; a medical historical past of myocardial infarction or unstable angina inside 6 months earlier than enrollment; or a mean QTcF prolongation to higher 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 growth 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 opposed results (TEAEs) and critical AEs; and figuring out the utmost tolerated dose and beneficial section 2 dose. Section 2’s major finish factors encompass the speed of TEAEs and critical AEs; and goal response charge 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://buyers.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
