Pivotal New Data from Merck’s Broad Oncology Portfolio at ESMO 2019 Congress

Phase 3 Data for KEYTRUDA^® (pembrolizumab) as Neoadjuvant Therapy in Combination with Chemotherapy in Patients with Triple-Negative Breast Cancer (KEYNOTE-522) to be Featured in ESMO Presidential Symposium and Official Press Program

Data for LYNPARZA Included in ESMO Presidential Symposium and Official Press Program: in Metastatic Castration-Resistant Prostate Cancer (PROfound) and in Advanced Ovarian Cancer (PAOLA-1)

KENILWORTH, N.J.–(BUSINESS WIRE)–$MRK #MRK–Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced new data from its broad oncology portfolio and pipeline will be presented at the European Society for Medical Oncology (ESMO) 2019 Congress in Barcelona, Spain, from Sept. 27-Oct. 1, 2019. More than 80 abstracts involving Merck cancer medicines and investigational candidates will be featured at the congress, spanning over 18 tumor types. Three of these abstracts – KEYTRUDA data in triple-negative breast cancer (TNBC), LYNPARZA data in prostate cancer and LYNPARZA data in ovarian cancer – were selected for inclusion in the ESMO Presidential Symposium sessions.

“The breadth of data to be presented at ESMO reflect our company’s commitment to advance KEYTRUDA and the other medicines in our portfolio across cancer types and stages of disease to help improve outcomes for cancer patients,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “Five years ago, KEYTRUDA received its first worldwide approval, and today new KEYTRUDA data will be presented at ESMO across more than 15 types of cancer, including first-time results in triple-negative breast cancer, in addition to new data for LYNPARZA, LENVIMA and our investigational candidates.”

Key abstracts to be presented at ESMO include:

• First presentation of results from the pivotal Phase 3 KEYNOTE-522 trial evaluating KEYTRUDA in combination with chemotherapy as neoadjuvant therapy in patients with TNBC, which will be featured in the ESMO Presidential Symposium and Press Program (Abstract #LBA8). As previously announced, KEYNOTE-522 met one of the dual primary endpoints of pathological complete response (pCR) following the neoadjuvant part of the neoadjuvant/adjuvant study regimen in patients with TNBC. Based on an interim analysis, KEYTRUDA in combination with chemotherapy demonstrated a statistically significant improvement in pCR rates compared with chemotherapy alone, regardless of PD-L1 status.

• First presentation of results from the Phase 3 PROfound trial evaluating Merck and AstraZeneca’s PARP inhibitor LYNPARZA in patients with metastatic castration-resistant prostate cancer (mCRPC) selected for BRCA 1/2 or ATM gene mutations, a subpopulation of homologous recombination repair gene mutations (HRRm), and who have progressed on prior treatment with new hormonal anticancer treatments. These data will be featured in the ESMO Presidential Symposium and Press Program (Abstract #LBA12). As previously announced, the PROfound trial met its primary endpoint, showing a statistically significant and clinically meaningful improvement in radiographic progression-free survival compared to enzalutamide or abiraterone.
• First presentation of results from the Phase 3 PAOLA-1 trial evaluating LYNPARZA plus bevacizumab as maintenance therapy in patients with advanced ovarian cancer who responded to first-line platinum-based chemotherapy and bevacizumab, which will be featured in the ESMO Presidential Symposium and Press Program (Abstract #LBA2). As previously announced, PAOLA-1 met its primary endpoint, significantly reducing the risk of disease progression or death in women taking LYNPARZA plus bevacizumab versus those taking bevacizumab alone.
• First presentation of final results from the endometrial cohort from the Phase 1b/2 KEYNOTE-146/Study 111 trial evaluating KEYTRUDA plus LENVIMA in patients with advanced endometrial carcinoma (Abstract #994O) (in collaboration with Eisai).
• Presentation of final results from the pivotal Phase 3 KEYNOTE-407 study evaluating KEYTRUDA plus chemotherapy in patients with metastatic squamous non-small cell lung cancer (NSCLC) (Abstract #LBA82).
• Initial results from the KEYNOTE-869/EV-103 trial evaluating KEYTRUDA plus enfortumab vedotin in locally advanced or metastatic urothelial cancer (Abstract #901O).
• A first-in-human Phase 1/2 trial of the oral HIF-2a inhibitor PT2977 in patients with advanced renal cell carcinoma (RCC) (Abstract #911PD). PT2977 is now part of Merck’s broad early stage oncology pipeline following the acquisition of Peloton Therapeutics.

Details on Abstracts Listed Above & Other Late-breaking and/or Proffered Paper Sessions

KEYTRUDA

Breast Cancer

• Abstract #LBA8, Proffered Paper Session: KEYNOTE-522: Phase 3 Study of Pembrolizumab (Pembro) + Chemotherapy (Chemo) vs Placebo (Pbo) + Chemo as Neoadjuvant Treatment, Followed by Pembro vs Pbo as Adjuvant Treatment for Early Triple-Negative Breast Cancer (TNBC). P. Schmid. Sunday, September 29, 5:15-5:30 p.m. CEST. Location: Barcelona Auditorium (Hall 2).
• Abstract #LBA21, Proffered Paper Session: KEYNOTE-119: Phase 3 Study of Pembrolizumab (Pembro) Versus Single-Agent Chemotherapy (Chemo) for Metastatic Triple-Negative Breast Cancer (mTNBC). J. Cortés. Saturday, September 28, 10:27-10:39 a.m. CEST. Location: Barcelona Auditorium (Hall 2).

Lung Cancer

• Abstract #LBA82, Poster Discussion Session: Pembrolizumab (Pembro) + Chemotherapy (Chemo) in Metastatic Squamous NSCLC: Final Analysis and Progression After the Next Line of Therapy (PFS2) in KEYNOTE-407. L. Paz-Ares. Sunday, September 29, 4:30-5:45 p.m. CEST (poster). 4:30 p.m. CEST (discussion). Location: Cordoba Auditorium (Hall 7).
• Abstract #1482O, Proffered Paper Session: Outcomes with Pembrolizumab (Pembro) Monotherapy in Patients (Pts) with PD-L1–Positive NSCLC with Brain Metastases: Pooled Analysis of KEYNOTE-001, -010, -024, and -042. A. Mansfield. Monday, September 30, 9:30-9:45 a.m. CEST. Location: Madrid Auditorium (Hall 2).
• Abstract #LBA79, Proffered Paper Session: Association Between Tissue TMB (tTMB) and Clinical Outcomes with Pembrolizumab Monotherapy (Pembro) in PD-L1-Positive Advanced NSCLC in the KEYNOTE-010 and -042 trials. R. Herbst. Friday, September 27, 4:39-4:51 p.m. CEST. Location: Barcelona Auditorium (Hall 2).
• Abstract #LBA80, Proffered Paper Session: Pembrolizumab (Pembro) Plus Platinum-Based Chemotherapy (Chemo) for Metastatic NSCLC: Tissue TMB (tTMB) and Outcomes in KEYNOTE-021, 189, and 407. L. Paz-Ares. Friday, September 27, 4:51-5:03 p.m. CEST. Location: Barcelona Auditorium (Hall 2).

Solid Tumors

• Abstract #440O, Proffered Paper Session: Phase 1 Study of the Arginase Inhibitor INCB001158 (1158) Alone and in Combination with Pembrolizumab (Pem) in Patients (Pts) with Advanced/Metastatic (Adv/Met) Solid Tumors. A. Naing. Sunday, September 29, 4:56-5:06 p.m. CEST. Location: Malaga Auditorium (Hall 5).
• Abstract #1192O, Proffered Paper Session: Association of Tumor Mutational Burden with Outcomes in Patients with Select Advanced Solid Tumors Treated with Pembrolizumab in KEYNOTE-158. A. Marabelle. Monday, September 30, 10:30-10:45 a.m. CEST. Location: Barcelona Auditorium (Hall 2).

Microsatellite Instability High (MSI-H) Cancers

• Abstract #1174O, Proffered Paper Session: Pembrolizumab in Microsatellite Instability High Cancers: Updated Analysis of the Phase 2 KEYNOTE-164 and KEYNOTE-158 Studies. L. Diaz. Monday, September 30, 10:45-11:00 a.m. CEST. Location: Barcelona Auditorium (Hall 2).

Gastric Cancers

• Abstract #LBA44, Proffered Paper Session: Pembrolizumab with or without Chemotherapy vs Chemotherapy in Patients with Advanced G/GEJ Cancer (GC) Including Outcomes According to Microsatellite Instability-High (MSI-H) Status in KEYNOTE-062. K. Shitara. Sunday, September 29, 11:15-11:30 a.m. CEST. Location: Madrid Auditorium (Hall 2).
• Abstract #LBA45, Poster Discussion Session: Health-Related Quality of Life (HRQoL) Impact of Pembrolizumab (P) Versus Chemotherapy (C) as First-Line (1L) Treatment in PD-L1–Positive Advanced Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma. E. Van Cutsem. Saturday, September 28, 4:30-5:50 p.m. CEST (poster). 4:50 p.m. CEST (discussion). Location: Tarragona Auditorium (Hall 7).

Skin Cancer

• Abstract #LBA72, Poster Discussion Session: Pembrolizumab for Recurrent/Metastatic Cutaneous Squamous Cell Carcinoma (cSCC): Efficacy and Safety Results From the Phase 2 KEYNOTE-629 Study. J. Grob. Saturday, September 28, 2:45-4:00 p.m. CEST (poster). 3:02 p.m. CEST (discussion). Location: Granada Auditorium (Hall 3).

LYNPARZA (olaparib) (in collaboration with AstraZeneca)

Prostate Cancer

• Abstract #LBA12, Proffered Paper Session: PROfound: Phase 3 Study of Olaparib Versus Enzalutamide or Abiraterone for Metastatic Castration-Resistant Prostate Cancer (mCRPC) with Homologous Recombination Repair (HRR) Gene Alterations. M. Hussain. Monday, September 30, 5:09-5:21 p.m. CEST. Location: Barcelona Auditorium (Hall 2).

Ovarian Cancer

• Abstract #LBA2, Proffered Paper Session: Phase 3 PAOLA-1/ENGOT-ov25 Trial: Olaparib plus Bevacizumab (Bev) as Maintenance Therapy in Patients (Pts) with Newly Diagnosed, Advanced Ovarian Cancer (OC) Treated with Platinum-Based Chemotherapy (PCh) Plus Bev. I. Ray-Coquard. Saturday, September 28, 4:42-4:54 p.m. CEST. Location: Barcelona Auditorium (Hall 2).

KEYTRUDA + LENVIMA (lenvatinib) (in collaboration with Eisai)

Endometrial Cancer

• Abstract #994O, Proffered Paper Session: Lenvatinib (LEN) and Pembrolizumab (PEMBRO) in Advanced Endometrial Cancer (EC). V. Makker. Sunday, September 29, 9:30-9:45 a.m. CEST. Location: Madrid Auditorium (Hall 2).

Pipeline/Early Oncology

Bladder Cancer

• Abstract #901O, Proffered Paper Session: EV-103: Initial Results of Enfortumab Vedotin Plus Pembrolizumab for Locally Advanced or Metastatic Urothelial Carcinoma. C. Hoimes. Saturday, September 28, 9:15-9:30 a.m. CEST. Location: Barcelona Auditorium (Hall 2).

Renal Cell Carcinoma

• Abstract #911PD, Poster Discussion Session: A First-in-Human Phase 1/2 Trial of the Oral HIF-2a Inhibitor PT2977 in Patients with Advanced RCC. E. Jonasch. Sunday, September 29, 3:00-4:15 p.m. CEST (poster). 3:35 p.m. CEST (discussion). Location: Pamplona Auditorium (Hall 2).

For more information, including a complete list of abstract titles and presentation dates and times for Merck’s oncology portfolio and pipeline, please visit the ESMO website at https://cslide.ctimeetingtech.com/esmo2019/attendee/confcal.

About KEYTRUDA^® (pembrolizumab) Injection, 100mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,000 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

KEYTRUDA^® (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) ≥1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for the treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [CPS ≥10] as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

• solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
• colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grade 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination with Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination with Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%), receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency), thyroid function (prior to and periodically during treatment), and hyperglycemia. For hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or 4 hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate.

Contacts

Media Contacts:

Pamela Eisele

(267) 305-3558

Kristen Drake

(908) 740-167

Investor Contacts:

Peter Dannenbaum

(908) 740-1037

Courtney Ronaldo

(908) 740-613

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