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ASCO Abstract #
Bintrafusp alfa (bifunctional fusion protein): TPS9114; Tepotinib (MET kinase inhibitor): 9005; Discovery: 2567; ERBITUX(R) (cetuximab): 3580; BAVENCIO(R) (avelumab): 9569; 101; 4552; 4072
– New biomarker analyses for BAVENCIO(R)* (avelumab) in combination with axitinib in first-line renal cell carcinoma (RCC)
– Data presented across several modalities and mechanisms showcase the scientific innovation and diversity of the company’s pipeline, which includes bintrafusp alfa~ (M7824) and tepotinib^
Merck, a leading science and technology company, today announced that data across several modalities and mechanisms targeting difficult-to-treat cancers will be presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, May 31-June 4, Chicago, IL, US. New data will be presented for BAVENCIO(R)* (avelumab) and ERBITUX(R) (cetuximab), including rational combinations with chemotherapy, radiation therapy and other targeted agents to try to identify new ways to improve patient outcomes. This includes an oral presentation of data defining biomarkers that differentiate therapy-specific outcomes in patients with advanced renal cell carcinoma (RCC), and who have been treated first-line with BAVENCIO(R) (avelumab) in combination with axitinib. Abstracts also showcase the scientific innovation and diversity of Merck’s pipeline, with results from a number of high-priority clinical development programs, including tepotinib^, bintrafusp alfa~ (M7824) and the company’s comprehensive DNA Damage Response (DDR) portfolio.
“At this year’s ASCO meeting we continue to demonstrate the breadth and depth of our oncology and immuno-oncology portfolio. We will present examples of the latest precision medicine and biomarker research and some of the most exciting mechanisms being investigated today, including tepotinib and our first-in-class bifunctional fusion protein immunotherapy, bintrafusp alfa,” said Luciano Rossetti, Global Head of Research & Development for the Biopharma business of Merck. “Merck’s oncology pipeline has significant promise in the near term through our late-stage priority programs, and our early pipeline includes several potentially groundbreaking modalities. We look forward to sharing the latest science with the global oncology community.”
For BAVENCIO(R) (avelumab), Merck will share data from five studies across tumor types including Merkel cell carcinoma, RCC, hepatocellular carcinoma and urothelial carcinoma. This includes an oral presentation of biomarker analyses of baseline tumor samples from the Phase III JAVELIN Renal 101 trial in previously untreated patients with advanced RCC. The trial indicated that PD-L1 expression (equal-to-or-less-than 1% immune cells) was associated with the longest progression-free survival (PFS) in the avelumab plus axitinib arm and the shortest PFS in the sunitinib arm (HR, 0.63; 95% CI, 0.49, 0.81). An analysis of relevant gene expression signatures (GES) indicated that in the avelumab plus axitinib arm, PFS was enhanced in immune GES-positive patients vs those in the negative group (HR, 0.63; 95% CI, 0.46, 0.86; 2-sided p=0.004), and vs those in an independent dataset (JAVELIN Renal 100; Choueiri, Lancet Oncol, 2018) (HR, 0.46; 95% CI, 0.20, 1.05; 2-sided p=0.064). The combination demonstrated a safety and tolerability profile consistent with the known safety profiles of each drug alone. The most common adverse reactions (equal-to-or-less-than 20%) were diarrhea, fatigue, hypertension, musculoskeletal pain, nausea, mucositis, palmar-plantar erythrodysesthesia, dysphonia, decreased appetite, hypothyroidism, rash, hepatotoxicity, cough, dyspnea, abdominal pain, and headache. Serious adverse reactions occurred in 35% of patients receiving BAVENCIO(R) (avelumab) in combination with axitinib. The incidence of major adverse cardiovascular events (MACE) was higher with BAVENCIO(R) (avelumab) in combination with axitinib vs sunitinib.
ERBITUX(R) (cetuximab) data from a retrospective analysis of overall survival by subsequent therapy in patients with RAS wild-type metastatic colorectal cancer from the Phase III EPIC study will be presented, to evaluate the effect of post-study therapies (with ERBITUX(R) without ERBITUX(R), or no subsequent therapy) on OS.
A number of the molecules to be featured were discovered in-house at Merck. This includes tepotinib, an oral MET inhibitor designed to inhibit the oncogenic MET receptor signaling caused by MET (gene) alterations, and bintrafusp alfa, a bifunctional fusion protein designed to simultaneously target two immuno-suppressive pathways. Merck’s partnership with GSK to jointly develop and commercialize bintrafusp alfa, announced in February 2019, is part of the company’s strategic approach to oncology R&D. Together, Merck and GSK aim to rapidly and efficiently progress this molecule, which represents a potential step change in the treatment of cancer.
For tepotinib, promising updated results from the ongoing Phase II VISION study in 85 patients with non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutations (identified by liquid biopsy [LBx] or tumor biopsy [TBx]) will be shared. Results show an overall response rate (ORR) of 51.4% for LBx patients (independent review committee [IRC]-assessed) or 63.9% (investigator-assessed). The ORR for TBx patients was 41.5% (IRC-assessed) or 58.5% (investigator-assessed). Median duration of response was 9.8 (IRC-assessed) or 17.1 months (investigator-assessed) for LBx patients and 12.4 (IRC-assessed) or 14.3 months (investigator-assessed) for TBx patients. Any grade treatment-related adverse events (TRAEs) reported by equal-to-or-less-than 10% of 69 patients evaluable for safety were peripheral edema (47.8%), diarrhea (18.8%), nausea (15.9%) and asthenia (10.1%). No Grade 4 or 5 TRAEs were observed. TRAEs led to permanent discontinuation in two (2.9%) patients (one interstitial lung disease, one diarrhea and nausea). These data continue to mature, and an updated data cut from the VISION study will be given as an oral presentation at the ASCO meeting on Monday, June 3.
For bintrafusp alfa, a trial-in-progress poster will be shared on the open-label study of bintrafusp alfa vs pembrolizumab as a first-line treatment in patients with PD-L1-expressing advanced NSCLC.
Merck takes a personalized approach to R&D, and precision medicine has long been a priority. Abstracts being presented at ASCO also include biomarker research programs that aim to help identify the patients most likely to benefit from specific treatments so they can achieve the best possible medical outcomes.
*The combination of BAVENCIO and axitinib is approved for the first-line treatment of advanced RCC only in the United States. There is no guarantee that avelumab in combination with axitinib will be approved for RCC by any other health authority worldwide.
^Tepotinib is the recommended International Nonproprietary Name (INN) for the MET kinase inhibitor (MSC2156119J). Tepotinib is currently under clinical investigation and not approved for any use anywhere in the world.
~Bintrafusp alfa is the proposed International Nonproprietary Name (INN) for the bifunctional immunotherapy M7824. Bintrafusp alfa is currently under clinical investigation and not approved for any use anywhere in the world.
