MedNess: bite-size biopharma and medtech news

Merck KGgA and GSK scrap bintrafusp alfa clinical development agreement
On 30^th September, Merck and GSK mutually agreed to axe their collaboration on bintrafusp alfa’s (anti-TGF-β x PD-L1 bispecific) clinical development.
Details: The decision, which came into effect on 30^th September, was based on a series of failures shown in bintrafusp alfa clinical trials and the lacklustre data generated, particularly in the Phase 3 INTR@PID Lung 037 study evaluating bintrafusp alfa versus pembrolizumab as frontline treatment for PD-L1+ NSCLC patients. In January 2021, trial failed to replicate encouraging data observed in other studies and was discontinued after IDMC’s recommendation.
Therefore, Merck did not receive any milestone payments from GSK and the latter is not liable for any future milestone obligations. In 2019, Merck and GSK had announced a global alliance, worth $4.2 billion, to co-develop and co-commercialize the asset in various oncology indications. The deal triggered an upfront payment of nearly $400m to Merck.
In August 2021, the asset failed in its third trial as 1L treatment for BTC patients in the phase 2/3 INTR@PID BTC 055. Earlier, in Jan and Mar, bintrafusp alfa showed disappointing results in the Phase 3 INTR@PID Lung 037 and Phase 2 INTR@PID BTC 047 investigating it as a 2^nd line asset in BTC, respectively.
Implications: The decision is a major blow, especially for GSK, which looked to strengthen its position in the oncology business. Merck will terminate several remaining bintrafusp trials in lung cancer, breast cancer and urothelial cancer except one trial in cervical cancer. The INTR@PID clinical program is expected to deepen Merck’s understanding of TGF-β and help guide future development of therapies targeting this pathway.

FDA Expands ERBITUX® (cetuximab) Label with Combination of BRAFTOVI® (encorafenib) for the Treatment of BRAF V600E Mutation+ve mCRC after Prior Therapy
"The BEACON study showed that the combination of ERBITUX and encorafenib significantly improved overall survival in patients with metastatic colorectal cancer with a BRAF V600E mutation – a subtype that typically has worse outcomes compared to those without the mutation," said David Hyman, M.D., chief medical officer, oncology at Lilly. "We are grateful to Pfizer for their collaboration as we've worked to bring this treatment regimen to patients."

FDA grants Priority Review for investigational targeted radioligand therapy 177Lu-PSMA-617 for patients with mCRPC

• FDA accepted and granted Priority Review to the NDA for 177Lu-PSMA-617, an investigational targeted radioligand therapy for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in the post androgen receptor pathway inhibition, post taxane-based chemotherapy setting.
• With Priority Review, the Prescription Drug User Fee Act (PDUFA) date is anticipated in the first half of 2022.
• Priority Review is based on positive data from the pivotal, Ph 3 VISION study showing 177Lu-PSMA-617 + standard of care (SOC), significantly improved OS and rPFS for men with progressive PSMA-positive mCRPC compared to SOC alone.
• Two additional studies with 177Lu-PSMA-617 in earlier lines of treatment for metastatic prostate cancer are ongoing, investigating clinical utility in the pre-taxane setting (PSMAfore) and in the metastatic hormone-sensitive setting (PSMAddition).
• The FDA previously granted Breakthrough Therapy designation for 177Lu-PSMA-617 for the treatment of mCRPC. Data from the VISION study were published in The New England Journal of Medicine (NEJM)2. Novartis is also evaluating additional opportunities to investigate 177Lu-PSMA-617 in earlier stages of prostate cancer.

Last Patient Enrolled in Ph 2 MOUNTAINEER Trial Evaluating TUKYSA® (Tucatinib) Regimen in HER2-Positive Metastatic Colorectal Cancer
“Completing enrollment in the MOUNTAINEER trial is an important step toward potentially bringing this therapy to patients with HER2-positive metastatic colorectal cancer,” said Roger D. Dansey, M.D., Chief Medical Officer, Seagen. “We previously expanded the size of this trial, with the intention of supporting registration under accelerated approval regulations in the United States. We look forward to receiving the trial results to potentially address a significant unmet medical need for patients.”

Deep learning enhances cancer diagnostic tools
Optical coherence tomography, a clinically common procedure that is used to generate high-resolution cross-sectional images of specific regions in the human body. The scientists at Beckham Institute Biophotonics Imaging Laboratory have used a software tool to enhance the capabilities of the hardware-based OCT into PS-OCT (Polarization sensitive mode) without the added cost and complexity. According to Yi “Edwin” Sun, PhD candidate in electrical and computer engineering at the University of Illinois Urbana-Champaign and member of the Beckman Institute’s Biophotonics Imaging Laboratory: “By adding a deep learning model on top of an OCT system, suddenly we arrive at PS-OCT capabilities without the traditional added hardware.”
OCT alone can detect the nature of tissues through a non-invasive use of light waves, while PS-OCT can detect abnormalities in microstructural features, e.g., collagen fiber orientations: a discernible change undergone in cancerous vs. normal tissue. Sun adds: ““Deep learning enabled a more advanced method of picking up subtle features in images, which can be used for more accurate segmentation and classification. It also allows the imaging tool to use multiple layers to pick up spatial features in an image.” With the use of historical data run through predictive analysis tools, Deep learning in PS-OCT can provide a commercial and clinical tool to accurately diagnose cancer.