intismeran autogene (mRNA-4157) / Merck (MSD), Moderna - LARVOL DELTA

Moderna Reports First Quarter 2025 Financial Results… (Moderna Press Release) - "COVID-19: The Company reported $84 million in Spikevax sales in the first quarter of 2025, which includes $29 million of U.S. sales and $55 million of international sales. As previously reported, Moderna entered into a tender opportunity in January to compete for COVID vaccine business in the EU; RSV: The Company reported $2 million in mRESVIA sales in the first quarter of 2025. Moderna's RSV vaccine for adults aged 60 years and older has been recently approved in Australia, Switzerland, Taiwan and the UK....Research and development expenses for the first quarter of 2025 decreased by 19% to $856 million, compared to the first quarter in 2024. The decrease was primarily driven by lower clinical development costs across respiratory programs due to timing of trial activities and program wind-downs. This reduction was partially offset by increased investment in Moderna's individualized neoantigen therapy (mRNA-4157)...and norovirus programs."

Commercial • Sales • Bladder Cancer • Melanoma • Non Small Cell Lung Cancer • Novel Coronavirus Disease • Respiratory Syncytial Virus Infections

Dynamics of T cell and T cell receptor following mRNA-4157 (V940) plus pembrolizumab or pembrolizumab alone in resected melanoma from the mRNA-4157-P201 (KEYNOTE-942) trial (AACR 2025) - "Expansion of novel T cell clonotypes in peripheral blood was observed to a greater extent after mRNA-4157 + pembro compared to pembro alone, and the degree of novel expansion was associated with RFS."

IO biomarker • Melanoma • Oncology • Solid Tumor

Phase 3 INTerpath-009 study: Individualized neoantigen therapy V940 (mRNA-4157) plus pembrolizumab for resected stage II-IIIB (N2) NSCLC with incomplete pathological response to neoadjuvant immunochemotherapy (AACR 2025) - P3 | "Secondary endpoints include OS, distant metastasis-free survival, DFS after next-line therapy, lung cancer-specific survival, patient-reported outcomes, and safety. The first pt was screened on October 21, 2024, and recruitment is ongoing."

Clinical • IO biomarker • P3 data • Tumor-specific neoantigens • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1

INTerpath-004: A Study of Adjuvant V940 and Pembrolizumab in Renal Cell Carcinoma (V940-004). (clinicaltrials.gov) - P2 | N=272 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

A Clinical Study of V940 and BCG in People With Bladder Cancer (V940-011/INTerpath-011) (clinicaltrials.gov) - P2 | N=308 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Advancements in Melanoma Treatment: A Review of PD-1 Inhibitors, T-VEC, mRNA Vaccines, and Tumor-Infiltrating Lymphocyte Therapy in an Evolving Landscape of Immunotherapy. (PubMed, J Clin Med) - "PD-1/PD-L1 inhibitors such as pembrolizumab and nivolumab block immune checkpoints, promoting T-cell cytotoxic activity and improving overall survival in patients with advanced melanoma...mRNA vaccines, such as Moderna's mRNA-4157/V940, take advantage of malignant-cell-specific neoantigens to amplify the adaptive immune response while protecting healthy tissue...This review explores combination therapies such as PD-L1 inhibitors with mRNA vaccines, or TIL therapy, which aim to enhance treatment through synergistic approaches. Further research is required to optimize these combinations, address barriers preventing their use, and control adverse events."

Journal • Review • Tumor-infiltrating lymphocyte • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor

A Clinical Study of V940 and BCG in People With Bladder Cancer (V940-011/INTerpath-011) (clinicaltrials.gov) - P2 | N=308 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

Monotherapy • New P2 trial • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

David Braun, MD, on phase 2 trial of an individualized neoantigen therapy for RCC (Urology Times) - "In this video, David A. Braun, MD, PhD, describes background and design of the phase 2 INTerpath-004 trial (NCT06307431), which is assessing the safety and efficacy of a neoantigen targeting personalized cancer vaccine, V940, in patients with renal cell carcinoma."

Video • Renal Cell Carcinoma

Phase 1/2 INTerpath-005 study: V940 (mRNA-4157) plus pembrolizumab with or without enfortumab vedotin (EV) for resected high-risk muscle-invasive urothelial carcinoma (MIUC). (ASCO-GU 2025) - P1/2 | " Eligibility criteria for the perioperative cohort include age ≥18 years, diagnosis of MIBC (T2-T4aN0M0 or T1-T4aN1M0) with urothelial carcinoma histology, eligibility and willingness to undergo radical cystectomy (RC) + pelvic lymph node dissection (PLND), and cisplatin ineligibility. The primary end points are safety (perioperative cohort) and DFS per investigator assessment (adjuvant cohort). Secondary end points are pathologic complete response and pathologic downstaging (perioperative cohort); overall survival, distant metastasis–free survival per investigator, safety, and tolerability (adjuvant cohort)."

P1/2 data • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

INTerpath-004: A phase 2, randomized, double-blind study of adjuvant pembrolizumab (pembro) with V940 (mRNA-4157) or placebo for renal cell carcinoma (RCC). (ASCO-GU 2025) - P2 | "Efficacy will be assessed in all randomly assigned patients, and safety will be assessed in all patients who received ≥1 dose of study intervention. Recruitment is ongoing."

Clinical • P2 data • Genito-urinary Cancer • Oncology • Solid Tumor

ASCO GU 2025: INTerpath-004: A Phase 2, Randomized, Double-Blind Study of Adjuvant Pembrolizumab (Pembro) With V940 (mRNA-4157) or Placebo for Renal Cell Carcinoma (RCC) (UroToday) - "INTerpath-004 (NCT06307431) is a global, multicenter, randomized, double-blind, phase 2 trial designed to evaluate the efficacy and safety or adjuvant V940 plus pembrolizumab or placebo in participants with RCC who have undergone nephrectomy....A total of 272 patients will be randomly assigned in a 1:1 ratio to receive pembrolizumab (400 mg IV every 6 weeks for up to 9 cycles) in combination with either V940 (1 mg IM every 3 weeks for up to 9 doses) or placebo. Treatment will continue until unacceptable toxicity, disease recurrence, patient withdrawal, or an investigator’s decision. Randomization will be stratified by histology (clear cell vs. papillary) and disease risk (intermediate-high, high, or M1 NED)."

Trial status • Renal Cell Carcinoma

A Clinical Study of V940 Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005) (clinicaltrials.gov) - P1/2 | N=230 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Apr 2031 ➔ Oct 2031 | Trial primary completion date: Oct 2026 ➔ Apr 2027

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

INTerpath-007: A Study of (Neo)Adjuvant V940 and Pembrolizumab in Cutaneous Squamous Cell Carcinoma (V940-007). (clinicaltrials.gov) - P2/3 | N=1012 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting | Trial completion date: May 2033 ➔ Mar 2026 | Trial primary completion date: Apr 2029 ➔ Mar 2026

Enrollment closed • Monotherapy • Trial completion date • Trial primary completion date • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Morgan Stanley: Personalized cancer vaccines and ADCs will become the main catalysts for the tumor treatment industry in 2025 [Google translation] (Sina Corp) - "It is reported that in a mid-term trial of patients with surgically resected high-risk melanoma (stage III/IV), Moderna's personalized cancer vaccine mRNA-4157 (V940) combined with Merck's PD-1 inhibitor Keytruda can improve patient survival and show lasting efficacy. Morgan Stanley analyst Terence Flynn pointed out that Moderna is waiting for the key phase II interim data of this melanoma combination therapy in the fourth quarter of 25/26...BioNTech is expected to release updated Phase 3 data from its anti-CTLA-4 candidate BNT316 in NSCLC....In terms of anti-tigit therapy, Merck is waiting for phase 3 data on MK-7684A as a first-line combination therapy for non-small cell lung cancer..."

Clinical data • Melanoma • Non Small Cell Lung Cancer

Personalis Advances Business Strategy with Investment from Merck and Extends Collaboration with Moderna (Businesswire) - "Personalis, Inc...announced today agreements with long time collaborators Merck and Moderna that accelerate the advancement of the company’s business strategy. The company has received an investment from Merck, known as MSD outside the United States and Canada, and separately has signed a multi-year extension with Moderna to utilize Personalis’ ImmunoID NeXT Platform and technology for V940/mRNA-4157, an investigational individualized neoantigen therapy (INT), being jointly developed by Merck and Moderna....Merck has agreed to purchase $50 million of Personalis common stock in a private placement at a price of $3.56 per share, which was the last reported closing price of Personalis’ common stock as reported on The Nasdaq Global Market on December 18, 2024."

Commercial • Solid Tumor

A Study of Pembrolizumab (MK-3475) With or Without V940 in Participants With Non-small Cell Lung Cancer (V940-009/INTerpath-009) (clinicaltrials.gov) - P3 | N=680 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Adaptive phase 2/3 randomized study of neoadjuvant and adjuvant pembrolizumab with V940 (mRNA-4157) for resectable locally advanced cutaneous squamous cell carcinoma: INTerpath-007 (SITC 2024) - P2/3 | "Ethics Approval The protocol was approved by the appropriate ethics committee or institutional review board at each center, and the trial was conducted per Good Clinical Practice guidelines and in accordance with the principles of the Declaration of Helsinki. All patients provided written informed consent."

Clinical • Metastases • P2/3 data • Tumor mutational burden • Cutaneous Melanoma • Melanoma • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • TMB

A phase 1, open-label, multicenter study to assess the safety, tolerability, and immunogenicity of mRNA-4157 alone and in combination in participants with solid tumors (SITC 2024) - "Background Neoantigens are tumor-specific non-synonymous mutations in proteins that are processed and presented in major histocompatibility complex molecules, driving anti-tumor T-cell responses.1 mRNA-4157 is a novel mRNA-based individualized neoantigen therapy that encodes up to 34 neoantigens mediating specific anti-tumor T-cell activation.2 In adjuvant melanoma, INT plus pembrolizumab induced durable improvements in RFS & DMFS.3 Neoantigens have been seen in less immune-infiltrated, high-recurrence tumors such as PDAC, gastric/GEJ and NSCLC, and long-term survivors demonstrate neoantigen specific T-cell responses.4 5 We hypothesize that mRNA-4157 will invigorate specific T-cells, potentially delaying recurrence and minimizing micro-metastases, thus affecting patient outcome.mRNA-4157-P101 is a single arm study to evaluate safety, tolerability, immunogenicity, ctDNA, anti-tumor efficacy and exploratory biomarkers of mRNA-4157 combination in solid tumors (figure..."

Clinical • P1 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

An Exploratory Cost-Effectiveness Analysis of Cancer Vaccines in Combination With Current Immune Checkpoint Inhibitors Vs Immune Checkpoint Inhibitor Monotherapy: A Case Study for V940 in High-Risk Stage 3 Melanoma in the US (ISPOR-EU 2024) - "If V940 is priced similarly to pembrolizumab at list price, preliminary analyses indicate cost-effectiveness is achievable. As V940 is a combination therapy with pembrolizumab, price reductions in pembrolizumab improve cost-effectiveness. Further data when available from V940-001 are required to increase the reliability of this study."

Case study • Checkpoint inhibition • Clinical • Combination therapy • Cost effectiveness • HEOR • Monotherapy • Melanoma • Oncology • Solid Tumor

INTerpath-001: A Clinical Study of V940 Plus Pembrolizumab in People With High-Risk Melanoma (V940-001) (clinicaltrials.gov) - P3 | N=1089 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor

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 (MSD) Press Release) - "Merck...announced the initiation of INTerpath-009, a pivotal Phase 3 randomized clinical trial evaluating V940 (mRNA-4157), an investigational individualized neoantigen therapy (INT), in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, as adjuvant treatment for patients with resectable Stage II, IIIA or IIIB (N2) non-small cell lung cancer (NSCLC) who did not achieve a pathological complete response (pCR) after receiving neoadjuvant KEYTRUDA plus platinum-based chemotherapy. Global recruitment in INTerpath-009 has begun, and the first patients have now started enrolling in Canada."

Trial status • Non Small Cell Lung Cancer

A Clinical Study of V940 Treatment and Pembrolizumab in People With Bladder Cancer (V940-005/INTerpath-005) (clinicaltrials.gov) - P1/2 | N=230 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Phase classification: P2 ➔ P1/2

Phase classification • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

INTerpath-007: A phase II/III, adaptive, randomized study of neoadjuvant and adjuvant pembrolizumab (pembro) with V940 (mRNA-4157) for treatment of resectable locally advanced (LA) cutaneous squamous cell carcinoma (cSCC) (ESMO 2024) - P2/3 | "The key secondary end points are pathological complete response assessed by blinded independent central review (BICR) and overall survival. Other secondary end points include ORR per RECIST v1.1 by investigator assessment, pathological partial response by BICR, disease-free survival by investigator assessment, and safety."

Clinical • Metastases • P2/3 data • Tumor mutational burden • Cutaneous Melanoma • Melanoma • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • TMB

A Study of Pembrolizumab (MK-3475) With or Without V940 in Participants With Non-small Cell Lung Cancer (V940-009/INTerpath-009) (clinicaltrials.gov) - P3 | N=680 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P3 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Phase 2 INTerpath-005 Study: Pembrolizumab (pembro) + V940 (mRNA-4157) vs Pembro + Placebo (pbo) for Adjuvant Treatment of Patients (pts) With Resected High-Risk Muscle-Invasive Urothelial Carcinoma (MIUC) (DGU 2024) - P2 | "The efficacy and safety of adjuvant pembro + V940 vs pembro + pbo in pts with resected high-risk MIUC will be evaluated in the randomized, double-blind, global, phase 2 INTerpath-005 study (NCT06305767).Materials and Pts aged ≥18 years with predominant urothelial carcinoma and high-risk pathologic disease (ypT2-4a and/or ypN+ after neoadjuvant cisplatin-based chemotherapy [NAC]; pT3-4a and/or pN+ without NAC) after radical resection will be enrolled. The primary end point is investigator-assessed DFS. Secondary end points are overall survival, investigator-assessed distant metastasis-free survival, safety, and tolerability."

Clinical • P2 data • Melanoma • Oncology • Solid Tumor • Urothelial Cancer