Pembrolizumab by Merck for Small-Cell Lung Cancer: Likelihood of Approval

Pembrolizumab is under clinical development by Merck and currently in Phase III for Small-Cell Lung Cancer. According to GlobalData, Phase III drugs for Small-Cell Lung Cancer have a 40% phase transition success rate (PTSR) indication benchmark for progressing into Pre-Registration. GlobalData’s report assesses how Pembrolizumab’s drug-specific PTSR and Likelihood of Approval (LoA) scores compare to the indication benchmarks. Buy the report here.

GlobalData tracks drug-specific phase transition and likelihood of approval scores, in addition to indication benchmarks based off 18 years of historical drug development data. Attributes of the drug, company and its clinical trials play a fundamental role in drug-specific PTSR and likelihood of approval.

Pembrolizumab overview

Pembrolizumab (Keytruda) is an antineoplastic immunomodulating agent. Keytruda is formulated as solution, lyophilised powder for solution, solution concentrate for intravenous route of administration. Keytruda is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Keytruda as monotherapy is indicated for the treatment of advanced (unresectable or metastatic) melanoma in adults. Keytruda is also indicated for the treatment of patients with unresectable or metastatic melanoma who have not received prior treatment with ipilimumab. Keytruda is also indicated for the treatment of patients with unresectable or metastatic melanoma, for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by test with disease progression on or after platinum-containing chemotherapy, for the first-line treatment of patients with unresectable or metastatic melanoma, for the treatment of patients with unresectable or metastatic melanoma who have not received prior  treatment with ipilimumab, at a dose of 2 mg/kg every three weeks. Keytruda is indicated in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients whose tumors express PD-L1 and who have received at least one prior chemotherapy regimen. Keytruda is also indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma (HNSCC) (as second and first line therapy), in combination with platinum and FU for the first-line treatment of patients with metastatic or with unresectable, recurrent Head And Neck Cancer Squamous Cell Carcinoma (HNSCC), 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, for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression (tumor proportion score [TPS] of 50 percent or more) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, 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. Keytruda, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC, irrespective of PD-L1. Keytruda is also indicated as monotherapy for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy, as well as adults who are not eligible for any platinum-containing chemotherapy. It is also indicated for the treatment of metastatic transitional (urothelial) tract cancer and gastric cancer. It is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy and for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL) who have failed autologous stem cell transplant (ASCT) and brentuximab vedotin (BV), or who are transplant-ineligible and have failed BV, for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient: 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 a fluoropyrimidine, oxaliplatin, 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 two or more prior lines of therapy and for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD -L1 ( C PS ≥1) as determined by  an FDA -approved test. It is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib, as adjuvant treatment of adults with stage III melanoma and lymph node involvement who have undergone complete resection, and in combination with carboplatin and either paclitaxel or nab-paclitaxel, for the first-line treatment of adults with metastatic squamous non-small cell lung cancer (NSCLC), and for the treatment of metastatic non-squamous non-small cell lung cancer, in combination with pemetrexed and platinum chemotherapy, in adults with no EGFR or ALK genomic tumour aberrations, and no prior systemic chemotherapy treatment for metastatic cancer, also as first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations, and in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC), and 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, treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either in combination with platinum- and fluoropyrimidine-based chemotherapy, or as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test and also indicated as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, for the first-line treatment of patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 (combined positive score [CPS] ≥1.Keytruda is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy, and for the treatment of recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 [Combined Positive Score (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. Keytruda is also indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). 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) with disease progression after one or more prior lines of systemic therapy. Keytruda, in combination with lenvatinib, is indicated for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR, who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation, and is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. Keytruda is indicated for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer.Keytruda is indicated for the treatment of adult patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in-situ (CIS) with or without papillary tumours who are ineligible for or have elected not to undergo cystectomy. Keytruda is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation. Keytruda is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. KEYTRUDA (pembrolizumab) plus chemotherapy as neoadjuvant treatment, then continued as adjuvant monotherapy after surgery for locally advanced, or high-risk early-stage triple-negative breast cancer (TNBC).

Pembrolizumab is under development for the treatment of newly diagnosed classical Hodgkin lymphoma, squamous cell carcinoma of paranasal sinus and nasal cavity cancer, metastatic esophageal squamous cell carcinoma, thoracic esophageal squamous cell carcinoma (ESCC), recurrent head and neck cancer squamous cell carcinoma, metastatic pancreatic ductal adenocarcinoma, newly diagnosed high grade glioma, relapsed/refractory acute lymphoblastic leukemia, multiple myeloma (third line therapy), neuroendocrine tumors, metastatic liver cancer, newly diagnosed glioblastoma and gliosarcoma, advanced melanoma, merkel cell carcinoma, metastatic prostate cancer resistant to androgen deprivation, HIV infections, Kaposi sarcoma, head and neck squamous cell carcinoma (adjuvant), adenoid cystic carcinoma, laryngeal squamous cell carcinoma, oropharynx, peripheral nerve sheath tumor, hypopharynx, larynx, oral cavity (mouth) cancer, urethral cancer, ureter cancer, metastatic urothelial bladder cancer, metastatic colorectal cancer, leiomyosarcoma, recurrent meningioma, endometrial, thyroid, anaplastic thyroid cancer, salivary gland cancer, dedifferentiated liposarcoma, synovial sarcoma, Ewing sarcoma, osteosarcoma, chondrosarcoma, soft tissue sarcoma (first line therapy and second line therapy), metastatic renal cell carcinoma, renal cell carcinoma (first line therapy), metastatic gastric cancer, adenocarcinoma of the gastroesophageal junction, esophageal cancer, gastrointestinal stromal tumors, pancreatic cancer, pancreatic ductal adenocarcinoma, metastatic biliary tract cancer, malignant glioma, metastatic/breast cancer, malignant glioma, thymic carcinoma, neuroblastoma, myelodysplastic syndrome, diffuse large B cell lymphoma including primary mediastinal large B cell lymphoma, Richter syndrome, classical Hodgkin lymphoma, basal cell carcinoma, non-Hodgkin lymphoma, non-small cell lung cancer, small-cell lung cancer, B-cell lymphomas, mantle cell lymphoma, chronic lymphocytic leukemia, advanced pleural mesothelioma, primary CNS lymphoma (PCNSL), extranodal diffuse large B-cell lymphoma, gray-zone lymphoma, follicular lymphoma, nongerminomatous (nonseminomatous) germ cell tumors, germinomatous (seminomatous) germ cell tumors, epithelial ovarian, fallopian tube, primary peritoneal carcinoma, non muscle invasive bladder cancer (first line therapy), hepatocellular carcinoma (as first line and second line therapy),metastatic adenocarcinoma of the pancreas, small intestine cancer, gliosarcoma, anal cancer, mycosis fungoides, sezary syndrome, leptomeningeal carcinomatosis, chronic phase myelofibrosis, polycythemia vera, post-essential thrombocythemia myelofibrosis and primary myelofibrosis. It is also under development for the treatment of previously untreated locally recurrent inoperable or metastatic triple negative breast cancer and metastatic high grade neuroendocrine tumors (who have failed platinum based chemotherapy). It is under development for the treatment of T-cell lymphoma, peripheral T-cell lymphoma and cutaneous T-cell lymphoma, muscle-invasive bladder cancer, HER2 positive metastatic breast cancer, hormone receptor-positive(HR+), HER2-negative metastatic breast cancer, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphomas and natural killer cell lymphomas. It is under development for the treatment of spindle cell squamous cell carcinoma, giant cell carcinoma, gastroenteropancreatic neuroendocrine tumor (GEP-NETs), extrahepatic bile duct cancer, colon tumor, rectal tumor, cervical cancer, vulvar cancer. It is also under development for the treatment of neuroendocrine carcinomas of the lung, squamous non-small lung cancer, locally advanced cutaneous squamous cell carcinoma, vaginal cancer, cervical high grade squamous intraepithelial lesion (HSIL), uterine cancer and high grade HPV-related vulvar intraepithelial neoplasia, cervical intraepithelial neoplasia, high grade meningioma and leukoplakia such as erythroleukoplakia or proliferative verrucous leukoplakia and penile squamous cell carcinoma. It was also under development for the treatment of relapsed refractory multiple myeloma (Third line therapy), multiple myeloma (first and second line) and advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in Asian subjects who have progressed after failure of first-line therapy, and refractory acute myeloid leukemia. It is administered through subcutaneous route.It is under development also treatment of pneumonia,coronavirus disease (2019). It is under development for the treatment of human papillomavirus (HPV)-associated recurrent respiratory papillomatosis (RRP). Keytruda plus Lenvima indicated for the treatment of radically unresectable or metastatic renal cell carcinoma in the first-line setting. Keytruda as monotherapy is indicated for the treatment of the following MSI-H or dMMR tumours in adults with unresectable or metastatic colorectal cancer after previous fluoropyrimidine-based combination therapy, advanced or recurrent endometrial carcinoma, who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation, unresectable or metastatic gastric, small intestine, or biliary cancer, who have disease progression on or following at least one prior therapy. Keytruda, in combination with chemotherapy with or without bevacizumab, is indicated for the treatment of persistent, recurrent, or metastatic cervical cancer in adults whose tumours express PD-L1 with a CPS ≥ 1. Keytruda is indicated as monotherapy for the adjuvant treatment of adults and adolescents aged 12 years and older with stage IIB or IIC melanoma and who have undergone complete resection. Keytruda is indicated for the treatment of advanced (unresectable or metastatic) melanoma and stage III melanoma (as adjuvant treatment following complete resection) to include adolescent patients aged 12 years and older.

It was also under development for the treatment of adrenocortical carcinoma, administered as a softgel capsule. It was also under development for the treatment of nasopharyngeal cancer and homologous-recombination deficient (HRD) metastatic hormone refractory prostate cancer.

Keytruda is under development as an adjuvant treatment for patients with stage IB (≥4 centimeters), II or IIIA non-small cell lung cancer (NSCLC) following complete surgical resection.

Merck overview

Merck is a biopharmaceutical company focused on the discovery, development, manufacturing and marketing of prescription medicines, biologic therapies, vaccines and animal health products. It offers prescription products for therapy areas related to cardiovascular, cancer, immune disorders, infectious, respiratory and women’s diseases, and diabetes. The company provides animal health products such as vaccines, poultry products, livestock products and aquaculture products. Merck sells medicines to drug wholesalers, retailers, hospitals, government agencies and managed health care providers; and animal health products to veterinarians, distributors and animal producers. The company and its subsidiaries operate in the Americas, Europe, the Middle East, Africa, Asia Pacific, and Latin America. Merck is known as MSD outside the US and Canada and is headquartered in Kenilworth, New Jersey, the US.

For a complete picture of Pembrolizumab’s drug-specific PTSR and LoA scores, buy the report here.