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)
"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 (≥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 (≥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 ≥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.
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.
Notes to Editors
Key Merck-supported abstracts slated for presentation are listed below. In addition, a number of investigator-sponsored studies have been accepted (not listed).
Biomarker analyses from
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Tepotinib is currently being investigated in NSCLC and Merck is actively assessing the potential of investigating tepotinib in combination with novel therapies and other tumor indications.
About Bintrafusp Alfa (M7824)
About BAVENCIO(R) (avelumab)
BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody. BAVENCIO has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, BAVENCIO has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.1-3 BAVENCIO has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.3-5 In November 2014, Merck and Pfizer announced a strategic alliance to co-develop and co-commercialize BAVENCIO.
The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and about 10,000 patients evaluated across more than 15 different tumor types. These tumor types include RCC, gastric/gastro-esophageal junction cancer, head and neck cancer, Merkel cell carcinoma, non-small cell lung cancer, and urothelial carcinoma.
BAVENCIO approved Indications
In September 2017, the European Commission granted conditional marketing authorization for BAVENCIO as a monotherapy for the treatment of adult patients with metastatic Merkel cell carcinoma (MCC). BAVENCIO is currently approved for patients with MCC in more than 45 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.
BAVENCIO(R) (avelumab) in combination with axitinib is indicated in the US for the first-line treatment of patients with advanced renal cell carcinoma (RCC).
In the US, the FDA granted accelerated approval for BAVENCIO for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
BAVENCIO (R) Safety Profile from the EU Summary of Product Characteristics (SmPC)
The special warnings and precautions for use for BAVENCIO include infusion-related reactions and immune-related adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, and other adverse reactions).
The SmPC list of the most common adverse reactions in patients with solid tumors includes fatigue, nausea, diarrhea, decreased appetite, constipation, infusion-related reactions, and weight loss and vomiting.
Common adverse events (reported in at least 20% of patients) in patients receiving axitinib were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, hand-foot syndrome, weight decreased, vomiting, asthenia, and constipation.
About ERBITUX(R) (cetuximab)
Very commonly reported side effects with Erbitux(R) include acne-like skin rash, mild to moderate infusion-related reactions and hypomagnesemia.
Erbitux(R) has already obtained market authorization in 114 countries worldwide for the treatment of RAS wild-type metastatic colorectal cancer and for the treatment of squamous cell carcinoma of the head and neck. Merck licensed the right to market Erbitux(R), a registered trademark of ImClone LLC, outside the U.S. and Canada from ImClone LLC, a wholly owned subsidiary of Eli Lilly and Company, in 1998.
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