Merck and Moderna Initiate Phase 3 Trial Evaluating Adjuvant V940 (mRNA-4157) in Combination with KEYTRUDA® (pembrolizumab) After Neoadjuvant KEYTRUDA and Chemotherapy in Patients With Certain Types of Non-Small Cell Lung Cancer (NSCLC)
Merck (MRK) and Moderna have initiated INTerpath-009, a Phase 3 clinical trial evaluating V940 (mRNA-4157) combined with KEYTRUDA for patients with resectable Stage II, IIIA or IIIB non-small cell lung cancer (NSCLC). The trial targets patients who didn't achieve complete response after neoadjuvant KEYTRUDA plus platinum-based chemotherapy. This marks the third Phase 3 trial for V940, focusing on earlier cancer stages. Patient enrollment has begun in Canada, expanding the companies' collaborative INTerpath clinical program which includes trials for melanoma, lung cancer, cutaneous squamous cell carcinoma, renal cell carcinoma, and urothelial carcinoma.
Merck (MRK) e Moderna hanno avviato INTerpath-009, uno studio clinico di Fase 3 che valuta V940 (mRNA-4157) combinato con KEYTRUDA per pazienti con cancro ai polmoni non a piccole cellule (NSCLC) resecabile di Stadio II, IIIA o IIIB. Lo studio è destinato a pazienti che non hanno ottenuto una risposta completa dopo il trattamento neoadiuvante con KEYTRUDA e chemioterapia a base di platino. Questo segna la terza sperimentazione di Fase 3 per V940, focalizzandosi su stadi precoci del cancro. L'arruolamento dei pazienti è iniziato in Canada, ampliando il programma clinico collaborativo INTerpath delle aziende, che include studi per melanoma, cancro ai polmoni, carcinoma a cellule squamose cutanee, carcinoma renale e carcinoma uroteliale.
Merck (MRK) y Moderna han iniciado el INTerpath-009, un ensayo clínico de Fase 3 que evalúa V940 (mRNA-4157) combinado con KEYTRUDA para pacientes con cáncer de pulmón no microcítico (NSCLC) resecable en etapas II, IIIA o IIIB. El ensayo se dirige a pacientes que no lograron una respuesta completa tras el tratamiento neoadyuvante con KEYTRUDA y quimioterapia basada en platino. Este es el tercer ensayo de Fase 3 para V940, centrándose en etapas más tempranas del cáncer. La inscripción de pacientes ha comenzado en Canadá, ampliando el programa clínico colaborativo INTerpath de las compañías, que incluye ensayos para melanoma, cáncer de pulmón, carcinoma de células escamosas cutáneas, carcinoma de células renales y carcinoma urotelial.
머크 (MRK)와 모더나는 절제 가능한 II, IIIA 또는 IIIB 단계의 비소세포 폐암(NSCLC) 환자를 위한 KEYTRUDA와 결합된 V940(mRNA-4157)를 평가하는 3상 임상시험 INTerpath-009을 시작했습니다. 이 시험은 네오아주반 KEYTRUDA와 백금계 항암화학요법 후 완전 반응에 도달하지 못한 환자를 대상으로 합니다. 이는 V940에 대한 세 번째 3상 시험으로, 초기 암 단계에 초점을 맞추고 있습니다. 환자 등록은 캐나다에서 시작되었으며, 이로써 여러 암에 대한 임상 시험을 포함한 두 회사의 협력 INTerpath 프로그램이 확장되었습니다. 이 프로그램은 흑색종, 폐암, 피부 편평세포암, 신세포암 및 요로상피암에 대한 시험을 포함합니다.
Merck (MRK) et Moderna ont lancé l'INTerpath-009, un essai clinique de phase 3 évaluant V940 (mRNA-4157) associé à KEYTRUDA pour des patients atteints de cancer du poumon non à petites cellules (NSCLC) résécable de stade II, IIIA ou IIIB. L'essai cible les patients n'ayant pas obtenu de réponse complète après un traitement néoadjuvant par KEYTRUDA et chimiothérapie à base de platine. Cela marque le troisième essai de phase 3 pour V940, se concentrant sur les stades précoces du cancer. L'enrôlement des patients a commencé au Canada, élargissant ainsi le programme clinique collaboratif INTerpath des entreprises, qui comprend des essais pour le mélanome, le cancer du poumon, le carcinome épidermoïde cutané, le carcinome à cellules rénales et le carcinome urothélial.
Merck (MRK) und Moderna haben INTerpath-009 gestartet, eine klinische Studie der Phase 3, die V940 (mRNA-4157) in Kombination mit KEYTRUDA bei Patienten mit resektablem nicht-kleinzelligem Lungenkrebs (NSCLC) im Stadium II, IIIA oder IIIB bewertet. Die Studie richtet sich an Patienten, die nach einer neoadjuvanten Therapie mit KEYTRUDA und platinhaltiger Chemotherapie keine vollständige Remission erzielt haben. Dies markiert die dritte Phase-3-Studie für V940, die sich auf frühere Krebsstadien konzentriert. Die Rekrutierung von Patienten hat in Kanada begonnen und erweitert das gemeinsame klinische Programm INTerpath der Unternehmen, das Studien zu Melanom, Lungenkrebs, kutanem Plattenepithelkarzinom, Nierenzellkarzinom und Urothelkarzinom umfasst.
- Expansion of clinical program with new Phase 3 trial
- Strategic collaboration with Moderna in multiple cancer types
- Patient enrollment already initiated in Canada
- None.
Insights
The initiation of the INTerpath-009 Phase 3 trial represents a significant milestone in personalized cancer treatment. The trial combines V940 (mRNA-4157), an individualized neoantigen therapy, with KEYTRUDA for NSCLC patients who didn't achieve complete response after initial treatment. This marks the third Phase 3 trial for this combination therapy.
The expansion into NSCLC is particularly notable as it's the leading cause of cancer deaths globally. The trial targets patients with Stage II, IIIA or IIIB (N2) disease, focusing on earlier intervention where treatment impact could be most significant. The broader INTerpath program now spans multiple cancer types, including melanoma, lung cancer and cutaneous squamous cell carcinoma, demonstrating strong momentum in mRNA-based cancer immunotherapy development.
The INTerpath-009 clinical trial demonstrates continued expansion of the INTerpath clinical program, as the third Phase 3 trial for the investigational individualized neoantigen therapy, V940 (mRNA-4157), focused on earlier stages of cancer
“While the overall survival rates for patients with non-small cell lung cancer have significantly improved in recent years, lung cancer continues to be the leading cause of cancer death worldwide,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “We are pleased to expand the INTerpath clinical trial program with Moderna, evaluating V940 (mRNA-4157), a promising new modality, in combination with KEYTRUDA to pursue meaningful advances for lung cancer and bring more options to patients with earlier stages of disease, where we potentially can have the most impact.”
“We are excited to build on our ongoing collaboration with our colleagues at Merck by expanding our research efforts for patients with NSCLC,” said Kyle Holen, M.D., Moderna's senior vice president and head of development, Therapeutics and Oncology. “We believe that our mRNA technology has the potential to improve the outcomes of those affected by lung cancer and together, INTerpath-002 and INTerpath-009 are designed to demonstrate this potential in early-stage lung cancer, with and without prior neoadjuvant therapy.”
Ongoing clinical development programs
Merck and Moderna have initiated Phase 3 randomized clinical trials evaluating mRNA-4157 (V940) in combination with KEYTRUDA as an adjuvant treatment in patients with resected high-risk (Stage IIB-IV) melanoma (INTerpath-001, NCT05933577) and non-small cell lung cancer (INTerpath-002, NCT06077760).
In 2024, Merck and Moderna also initiated a two-part Phase 2/3 randomized clinical trial evaluating mRNA-4157 (V940) in combination with KEYTRUDA as neoadjuvant and adjuvant treatment in patients with resectable locally advanced Stage II-IV (M0) cutaneous squamous cell carcinoma (INTerpath-007, NCT06295809), a Phase 2 randomized clinical trial evaluating mRNA-4157 (V940) in combination with KEYTRUDA as adjuvant treatment in patients with intermediate-high-risk, high-risk, or M1 no evidence of disease renal cell carcinoma (INTerpath-004, NCT06307431), and a Phase 2 randomized clinical trial evaluating mRNA-4157 (V940) in combination with KEYTRUDA as adjuvant treatment in patients with high-risk muscle-invasive urothelial carcinoma post-radical resection (INTerpath-005, NCT06305767).
About mRNA-4157 (V940)
mRNA-4157 (V940) is a novel investigational messenger RNA (mRNA)-based individualized neoantigen therapy (INT) consisting of a synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient’s tumor. Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity.
Individualized neoantigen therapies are designed to train and activate an antitumor immune response by generating specific T-cell responses based on the unique mutational signature of a patient’s tumor. KEYTRUDA is an immunotherapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. As previously announced from the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial evaluating patients with high-risk stage III/IV melanoma, combining mRNA-4157 (V940) with KEYTRUDA may provide a meaningful benefit over KEYTRUDA alone. Merck and Moderna continue to evaluate and expand the V940 INTerpath clinical development program for additional tumor types and treatment settings.
About INTerpath-009 (NCT06623422)
INTerpath-009 is a global, randomized, double-blind Phase 3 trial evaluating 680 patients with resected (R0 or R1) Stage II, IIIA, IIIB (N2) NSCLC who did not achieve a pCR after neoadjuvant KEYTRUDA plus platinum-based chemotherapy. Following surgical resection, participants 18 years and older will be randomized 1:1 to receive either V940 (mRNA-4157) (1 mg every three weeks for up to nine doses) and KEYTRUDA (400 mg every six weeks up to seven cycles) or placebo (1 mg every three weeks for up to nine doses) and KEYTRUDA (400 mg every six weeks up to seven cycles). The primary endpoint is disease-free survival (DFS), defined as the time from randomization to any recurrence (local, locoregional, regional, or distant), occurrence of new primary NSCLC, as assessed by the investigator, or death due to any cause, whichever occurs first. The secondary endpoints are overall survival (OS), distant metastasis-free survival (DMFS), DFS2, lung cancer-specific survival (LCSS), safety, and quality of life.
Key eligibility criteria for the trial include: patients who have histologically/cytologically confirmed diagnosis of Stage II, IIIA, or IIIB (N2) NSCLC (American Joint Committee on Cancer [AJCC] 8th Edition), have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, no pCR by local testing after neoadjuvant chemotherapy plus KEYTRUDA, completed surgery, with no disease by baseline imaging , and exclude epidermal growth factor receptor (EGFR) mutation.
For further information, please see the clinicaltrials.gov page for INTerpath-009.
About lung cancer
Lung cancer is the leading cause of cancer death worldwide. In 2022 alone, there were approximately 2.4 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer is the most common type of lung cancer, accounting for about
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (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 1,600 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.
Selected KEYTRUDA® (pembrolizumab) Indications in the
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) ≥
- 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 ≥
KEYTRUDA is indicated for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC.
See additional selected KEYTRUDA indications in the
Selected Important Safety Information for KEYTRUDA
Severe and Fatal Immune-Mediated Adverse Reactions
KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.
Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in
Pneumonitis occurred in
Pneumonitis occurred in
Immune-Mediated Colitis
KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in
Hepatotoxicity and Immune-Mediated Hepatitis
KEYTRUDA as a Single Agent
KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in
KEYTRUDA With Axitinib
KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently 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. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (
Immune-Mediated Endocrinopathies
Adrenal Insufficiency
KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in
Hypophysitis
KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in
Thyroid Disorders
KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in
Hyperthyroidism occurred in
Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis
Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in
Immune-Mediated Nephritis With Renal Dysfunction
KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in
Immune-Mediated Dermatologic Adverse Reactions
KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with anti– PD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in
Other Immune-Mediated Adverse Reactions
The following clinically significant immune-mediated adverse reactions occurred at an incidence of <
Infusion-Related Reactions
KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in
Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)
Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after anti–PD-1/PD-L1 treatments. Transplant- related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between anti–PD-1/PD-L1 treatments and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using anti–PD-1/PD-L1 treatments prior to or after an allogeneic HSCT.
Increased Mortality in Patients With Multiple Myeloma
In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an anti–PD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.
Embryofetal Toxicity
Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.
Adverse Reactions
In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-054, when KEYTRUDA was administered as a single agent to patients with stage III melanoma, KEYTRUDA was permanently discontinued due to adverse reactions in
In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in
In KEYNOTE-671, adverse reactions occurring in patients with resectable NSCLC receiving KEYTRUDA in combination with platinum-containing chemotherapy, given as neoadjuvant treatment and continued as single-agent adjuvant treatment, were generally similar to those occurring in patients in other clinical trials across tumor types receiving KEYTRUDA in combination with chemotherapy.
The most common adverse reactions (reported in ≥
In the neoadjuvant phase of KEYNOTE-671, when KEYTRUDA was administered in combination with platinum-containing chemotherapy as neoadjuvant treatment, serious adverse reactions occurred in
Of the KEYTRUDA-treated patients who received neoadjuvant treatment,
In the adjuvant phase of KEYNOTE-671, when KEYTRUDA was administered as a single agent as adjuvant treatment, serious adverse reactions occurred in
Adverse reactions observed in KEYNOTE-091 were generally similar to those occurring in other patients with NSCLC receiving KEYTRUDA as a single agent, with the exception of hypothyroidism (
In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in
In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-204, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-A39, when KEYTRUDA was administered in combination with enfortumab vedotin to patients with locally advanced or metastatic urothelial cancer (n=440), fatal adverse reactions occurred in
In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in
Adverse reactions occurring in patients with MSI-H or dMMR CRC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.
In KEYNOTE-158 and KEYNOTE-164, adverse reactions occurring in patients with MSI-H or dMMR cancer were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.
In KEYNOTE-811, when KEYTRUDA was administered in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-859, when KEYTRUDA was administered in combination with fluoropyrimidine- and platinum-containing chemotherapy, serious adverse reactions occurred in
In KEYNOTE-590, when KEYTRUDA was administered with cisplatin and fluorouracil to patients with metastatic or locally advanced esophageal or GEJ (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma who were not candidates for surgical resection or definitive chemoradiation, KEYTRUDA was discontinued due to adverse reactions in
Adverse reactions occurring in patients with esophageal cancer who received KEYTRUDA as a monotherapy were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.
In KEYNOTE-A18, when KEYTRUDA was administered with CRT (cisplatin plus external beam radiation therapy [EBRT] followed by brachytherapy [BT]) to patients with FIGO 2014 Stage III-IVA cervical cancer, fatal adverse reactions occurred in
In KEYNOTE-826, when KEYTRUDA was administered in combination with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab (n=307), to patients with persistent, recurrent, or first-line metastatic cervical cancer regardless of tumor PD-L1 expression who had not been treated with chemotherapy except when used concurrently as a radio- sensitizing agent, fatal adverse reactions occurred in
KEYTRUDA was discontinued in
For patients treated with KEYTRUDA, chemotherapy, and bevacizumab (n=196), the most common adverse reactions (≥
For patients treated with KEYTRUDA in combination with chemotherapy with or without bevacizumab, the most common adverse reactions (≥
In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-394, KEYTRUDA was discontinued due to adverse reactions in
In KEYNOTE-966, when KEYTRUDA was administered in combination with gemcitabine and cisplatin, KEYTRUDA was discontinued for adverse reactions in
In KEYNOTE-017 and KEYNOTE-913, adverse reactions occurring in patients with MCC (n=105) were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a single agent.
In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in
In KEYNOTE-564, when KEYTRUDA was administered as a single agent for the adjuvant treatment of renal cell carcinoma, serious adverse reactions occurred in
In KEYNOTE-868, when KEYTRUDA was administered in combination with chemotherapy (paclitaxel and carboplatin) to patients with advanced or recurrent endometrial carcinoma (n=382), serious adverse reactions occurred in
Adverse reactions occurring in patients with MSI-H or dMMR endometrial carcinoma who received KEYTRUDA as a single agent were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a single agent.
Adverse reactions occurring in patients with TMB-H cancer were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.
Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.
In KEYNOTE-522, when KEYTRUDA was administered with neoadjuvant chemotherapy (carboplatin and paclitaxel followed by doxorubicin or epirubicin and cyclophosphamide) followed by surgery and continued adjuvant treatment with KEYTRUDA as a single agent (n=778) to patients with newly diagnosed, previously untreated, high-risk early-stage TNBC, fatal adverse reactions occurred in
In KEYNOTE-355, when KEYTRUDA and chemotherapy (paclitaxel, paclitaxel protein-bound, or gemcitabine and carboplatin) were administered to patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting (n=596), fatal adverse reactions occurred in
Lactation
Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the last dose.
Pediatric Use
In KEYNOTE-051, 173 pediatric patients (65 pediatric patients aged 6 months to younger than 12 years and 108 pediatric patients aged 12 years to 17 years) were administered KEYTRUDA 2 mg/kg every 3 weeks. The median duration of exposure was 2.1 months (range: 1 day to 25 months).
Adverse reactions that occurred at a ≥
Geriatric Use
Of the 564 patients with locally advanced or metastatic urothelial cancer treated with KEYTRUDA in combination with enfortumab vedotin,
Additional Selected KEYTRUDA Indications in the
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with Stage IIB, IIC, or III melanoma following complete resection.
Malignant Pleural Mesothelioma
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of adult patients with unresectable advanced or metastatic malignant pleural mesothelioma (MPM).
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).
KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.
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. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
Urothelial Cancer
KEYTRUDA, in combination with enfortumab vedotin, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer.
KEYTRUDA, as a single agent, is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma:
- who are not eligible for any platinum-containing chemotherapy, or
- who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
KEYTRUDA, as a single agent, 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.
Microsatellite Instability-High or Mismatch Repair Deficient 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, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-approved test.
Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma 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 of this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Esophageal Cancer
KEYTRUDA is indicated for the 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.
Cervical Cancer
KEYTRUDA, in combination with chemoradiotherapy (CRT), is indicated for the treatment of patients with FIGO 2014 Stage III-IVA cervical cancer.
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (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 cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.
Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.
Biliary Tract Cancer
KEYTRUDA, in combination with gemcitabine and cisplatin, is indicated for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer (BTC).
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC).
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC).
KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.
Endometrial Carcinoma
KEYTRUDA, in combination with carboplatin and paclitaxel, followed by KEYTRUDA as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial carcinoma.
KEYTRUDA, as a single agent, is indicated for the treatment of adult patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.
Tumor Mutational Burden-High Cancer
KEYTRUDA 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.
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 TMB-H central nervous system cancers have not been established.
Cutaneous Squamous Cell Carcinoma
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.
Triple-Negative Breast Cancer
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, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
Merck’s focus on cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.
About Merck’s research in lung cancer
Merck is advancing research aimed at transforming the way lung cancer is treated, with a goal of improving outcomes for patients affected by this deadly disease. Through nearly 200 clinical trials evaluating more than 36,000 patients around the world, Merck is at the forefront of lung cancer research. In NSCLC, KEYTRUDA has six approved
About Merck
At Merck, known as MSD outside of
About Moderna
Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines.
Moderna’s mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
Moderna’s focus on cancer
At Moderna, we are delivering on the promise of mRNA science to create a new generation of transformative medicines for patients. We are relentlessly working to grow our cancer therapeutic modality by discovering mRNA medicines that harness the body’s immune system to identify and kill cancer cells in the same way the immune system identifies and targets infections. One example of a promising oncology candidate is the creation of individualized, mRNA-based cancer therapies. We also continue to strengthen our portfolio through strategic collaborations that increase our potential to improve treatment options for patients with cancer.
Forward-Looking Statement of Merck & Co., Inc.,
This news release of Merck & Co., Inc.,
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2023 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Moderna Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: Merck and Moderna’s Phase 3 trial evaluating mRNA-4157 in combination with KEYTRUDA in the adjuvant setting in patients with resectable Stage II, IIIA or IIIB (N2) non-small cell lung cancer (NSCLC) who did not achieve a pathological complete response after receiving neoadjuvant KEYTRUDA plus platinum-based chemotherapy; the companies’ planned comprehensive clinical development program and plans to expand to additional tumor types; the potential for mRNA, including mRNA-4157, to effectively treat different types of cancer; the potential of mRNA technology for lung cancer patients irrespective of treatment regimen and disease stage; the ability of an individualized neoantigen therapy to trigger a tailored antitumor response specific to a patient’s tumor mutation signature; and Moderna’s strategic collaborations to improve treatment options for patients with cancer. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna's control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others, those risks and uncertainties described under the heading "Risk Factors" in Moderna's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, filed with the
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Medication Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf.
View source version on businesswire.com: https://www.businesswire.com/news/home/20241028767283/en/
Merck Media:
Sienna Choi, (908) 873-4311
Julie Cunningham, (617) 519-6264
Moderna Media:
Luke Mircea-Willats
Senior Director, International Communications
Luke.mirceawillats@modernatx.com
Merck Investor:
Peter Dannenbaum, (732) 594-1579
Damini Chokshi, (732) 594-1577
Moderna Investor:
Lavina Talukdar
Senior Vice President & Head of Investor Relations
lavina.talukdar@modernatx.com
617-209-5834
Source: Merck & Co., Inc.
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