MK-3475 SC / Merck (MSD) - LARVOL DELTA

Participant-Reported Preference for Pembrolizumab Administered Subcutaneously or Intravenously: A Randomized, Open-Label, Phase II Study. (PubMed, JCO Oncol Pract) - P2 | "More participants preferred pembrolizumab SC over pembrolizumab IV and chose to continue with pembrolizumab SC. The results of this study suggest that pembrolizumab SC improves convenience compared with pembrolizumab IV in cancer treatment."

Journal • P2 data • Genito-urinary Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • PD-L1

Phase 3 Study of Adjuvant Subcutaneous MK-3475A Plus Calderasib or Placebo in Resected Stage IIA-IIIB (N2), KRAS G12Cm NSCLC (IASLC-WCLC 2026) - P3 | "MK-3475A is pembrolizumab with berahyaluronidase alfa (MK-5180), a variant of human hyaluronidase developed and manufactured by Alteogen Inc (Daejeon, South Korea) for subcutaneous (SC) administration. The phase 3 KANDLELIT-013 study (NCT07431827) evaluates adjuvant calderasib in combination with pembrolizumab SC in participants with completely resected, stage IIA-IIIB (N2), KRAS G12C-mutated NSCLC following receipt of neoadjuvant pembrolizumab plus chemotherapy or adjuvant chemotherapy...Secondary endpoints include OS, distant metastasis-free survival per investigator, lung cancer-specific survival, patient reported outcomes, and safety. Enrollment is projected to start in April 2026 at 210 global sites."

Clinical • IO biomarker • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • KRAS • PD-L1

A Phase 3 Trial of First-Line MK-3475A (Subcutaneous Pembrolizumab) for Stage IV NSCLC With PD-L1 TPS ≥ 50% (IASLC-WCLC 2025) - P3 | "Introduction : First-line treatment for patients with stage IV non-small-cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥50% and no targetable genetic alterations includes intravenous (IV) administration of the anti-PD-1 monoclonal antibody (mAb) pembrolizumab. Secondary objectives include exposure (cycle 1 maximum concentration [C max ] and C trough , and steady state [cycle 3] C max and AUC 0-6wk ) of pembrolizumab SC vs pembrolizumab IV Q6W, anti-pembrolizumab antibody levels, cycle 1 and steady-state (cycle 3) C trough of pembrolizumab SC vs pembrolizumab IV Q3W, ORR, PFS, and duration of response (each per RECIST v1.1 by blinded independent central review), OS, safety, and pt-reported outcomes. Recruitment is ongoing."

Clinical • IO biomarker • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • EGFR • ROS1

A Study to Evaluate ARV-6723 Alone and With Pembrolizumab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=499 | Recruiting | Sponsor: Arvinas Inc.

Monotherapy • New P1/2 trial • Oncology • Solid Tumor • CTLA4 • LAG3 • PD-1 • PD-L1

PHARMACOKINETICS, EFFICACY, AND SAFETY OF SUBCUTANEOUS PEMBROLIZUMAB IN RELAPSED OR REFRACTORY CLASSIC HODGKIN LYMPHOMA (CHL) OR PRIMARY MEDIASTINAL LARGE B-CELL LYMPHOMA (PMBCL): A PHASE 2 STUDY (EHA 2026) - P2 | "MK-3475A is pembrolizumab with berahyaluronidase alfa (MK-5180) for subcutaneous administration (subcutaneous pembrolizumab)...Participants with cHL had received ≥1 multiagent regimen, and participants with PMBCL had received ≥2 prior therapies (including ≥1 rituximab-based regimen)...Summary/Conclusion The PK profile of subcutaneous pembrolizumab in participants with hematologic tumors was similar to that in solid tumors and was consistent with the typical PK profile for subcutaneous monoclonal antibodies (Figure). Subcutaneous pembrolizumab at a dose of 790 mg Q6W showed a manageable safety profile and efficacy consistent with intravenous pembrolizumab."

Clinical • P2 data • PK/PD data • B Cell Lymphoma • Classical Hodgkin Lymphoma • Endocrine Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Musculoskeletal Pain • Primary Mediastinal Large B-Cell Lymphoma • Pruritus • Solid Tumor

Lenvatinib plus pembrolizumab versus standard of care in recurrent/metastatic head and neck squamous cell carcinoma: Randomized, phase 2 LEAP-009 trial. (PubMed, Eur J Cancer) - P2 | "Lenvatinib-pembrolizumab did not improve OS compared with SOC. More participants discontinued lenvatinib-pembrolizumab and lenvatinib monotherapy than SOC. Further research is needed to determine effective second-line treatments for this population."

Journal • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

BNT326-02: A Clinical Trial to Test if an Investigational Combination Therapy With BNT326 and BNT327 is Safe and Potentially Beneficial for People With Advanced Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1/2 | N=420 | Recruiting | Sponsor: BioNTech SE

Trial initiation date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • HER-2 • KRAS • MET • NTRK • RET • ROS1

KEYNOTE-603: Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone and in Combination in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=161 | Active, not recruiting | Sponsor: ModernaTX, Inc. | N=242 ➔ 161 | Trial completion date: Aug 2027 ➔ Nov 2027 | Trial primary completion date: Aug 2027 ➔ Nov 2027

Enrollment change • Trial completion date • Trial primary completion date • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

KEYNOTE-603: Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone and in Combination in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=242 | Active, not recruiting | Sponsor: ModernaTX, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Gastric Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR • TMB

Budget and Time Impact Analysis of Introducing Subcutaneous Pembrolizumab to Patients From Institution HCP and Patient Perspectives in the United States (US) (ISPOR-EU 2025) - "Pembrolizumab with berahyaluronidase alfa for subcutaneous (SC) administration demonstrated noninferior pharmacokinetics compared to pembrolizumab IV with consistent efficacy and safety results reported in the MK3475A-D77 trial. Pembrolizumab SC will enhance the drug administration of immunotherapy for healthcare providers, expecting to improve practice efficiency, mitigate capacity constraints, and save budget. It also provides benefits to patients in administration time saving and potential productivity gain."

Clinical

Model-based dose selection and pharmacokinetic bridging of subcutaneous from intravenous pembrolizumab across indications. (PubMed, Eur J Cancer) - P1, P3 | "These findings confirm pembrolizumab SC 790 mg Q6W and 395 Q3W are appropriate to maintain efficacy and safety similar to pembrolizumab IV across approved indications."

Journal • PK/PD data • Oncology

BNT326-02: A Clinical Trial to Test if an Investigational Combination Therapy With BNT326 and BNT327 is Safe and Potentially Beneficial for People With Advanced Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1/2 | N=420 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

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

A Time and Motion Study Comparing Subcutaneous Pembrolizumab Versus Intravenous Pembrolizumab in Combination with Chemotherapy for the Treatment of Metastatic Non-small Cell Lung Cancer. (PubMed, Adv Ther) - "Pembrolizumab SC substantially reduces active HCP time and patient chair time versus pembrolizumab IV. Time liberated for HCPs could be reallocated toward additional patient care activities, while optimized chair utilization could improve overall healthcare efficiency."

Clinical • Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Pharmacokinetics and bioavailability of pembrolizumab with berahyaluronidase alfa for subcutaneous administration in participants with advanced or metastatic solid tumors: The phase 1 study 3475A-C18. (PubMed, Eur J Cancer) - P1 | "Results from study 3475A-C18 informed selection of pembrolizumab SC 790 mg Q6W at 165 mg/mL for further clinical development to ensure that all patients have the appropriate pembrolizumab exposure to derive expected clinical benefit. Arm 4 results provided key clinical data supporting the pembrolizumab SC 395 mg Q3W dosing regimen."

Journal • P1 data • PK/PD data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

BNT326-02: A Clinical Trial to Test if an Investigational Combination Therapy With BNT326 and BNT327 is Safe and Potentially Beneficial for People With Advanced Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P1/2 | N=420 | Not yet recruiting | Sponsor: BioNTech SE

New P1/2 trial • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

KEYNOTE-603: Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone and in Combination in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=242 | Recruiting | Sponsor: ModernaTX, Inc. | Trial completion date: Jun 2025 ➔ Aug 2027 | Trial primary completion date: Jun 2025 ➔ Aug 2027

Trial completion date • Trial primary completion date • Gastric Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR • TMB

Subcutaneous Versus Intravenous Pembrolizumab, in Combination With Chemotherapy, for Treatment of Metastatic Non-Small Cell Lung Cancer: The Phase 3 3475A-D77 Trial. (PubMed, Ann Oncol) - P3 | "Overall exposure and trough concentrations of pembrolizumab SC 790 mg Q6W were noninferior to those of pembrolizumab IV 400 mg Q6W given with chemotherapy in participants with treatment-naïve mNSCLC. Results support pembrolizumab SC as a treatment option in all indications where pembrolizumab IV can be used."

Journal • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

ESMO 2024: Treatment of uHCC : Episode 7: LEAP-012 Study Results (OncLive) - "Panelists discuss the findings from the LEAP-012 study, which explores the efficacy of transarterial chemoembolization combined with lenvatinib and pembrolizumab in patients with Child-Pugh class A disease and intermediate-stage hepatocellular carcinoma."

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KEYNOTE-603: Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone and in Combination in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=242 | Recruiting | Sponsor: ModernaTX, Inc. | Active, not recruiting ➔ Recruiting | N=108 ➔ 242

Enrollment change • Enrollment open • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • ALK • EGFR • TMB

Relative Bioavailability Study of Subcutaneous Injection Versus Intravenous Infusion of Pembrolizumab (MK-3475) in Participants With Advanced Melanoma (MK-3475-555/KEYNOTE-555) (clinicaltrials.gov) - P1 | N=138 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Metastases • Trial completion • Melanoma • Oncology • Solid Tumor • BRAF • TNFRSF9

A Pilot Study of Pembrolizumab and Peptide Receptor Radionuclide Therapy for Patients with Metastatic Well Differentiated Neuroendocrine Tumors (NANETS 2023) - "Preliminary results indicate that combination treatment with 177Lu-DOTATATE PRRT and pembrolizumab is well tolerated and leads to durable disease control in a subset of patients."

Clinical

A Pilot Study of Pembrolizumab and Embolization or 90Y Radioembolization for Patients with Metastatic WellDifferentiated Neuroendocrine Tumors (NANETS 2023) - "Combination therapy with pembrolizumab and TAE or TARE did not lead to abscopal responses in a small group of patients with metastatic WD-NET."

Clinical

Neoadjuvant Vibostolimab Plus Pembrolizumab Demonstrates Activity in Melanoma (Cancer Therapy Advisor) - "These results support further investigation of vibostolimab plus pembrolizumab in the adjuvant and neoadjuvant settings, said study presenter Reinhard Dummer, MD..."

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Updates in the Treatment of Advanced Renal Cell Carcinoma : Episode 3: 4-Year Follow-Up Results of Lenvatinib Plus Pembrolizumab in Frontline aRCC (Cancer Network) - "Panelists analyze the 4-year follow-up results of the CLEAR study, covering study design, efficacy, safety, and clinical implications."

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Highlights in Renal Cell Carcinoma From ASCO 2023 (Medscape) - "Dr Eric Jonasch...highlights from the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting. First, Dr Jonasch discusses the CONTACT-03 study, which examined whether adding atezolizumab to cabozantinib would improve outcomes in patients who progressed on immunotherapy. The combination provided no clear benefit and led to increased toxicity."

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