gocatamig (MK-6070) / Merck (MSD), Daiichi Sankyo - LARVOL DELTA

A Clinical Study of Gocatamig (MK-6070) and Infinatamab Deruxtecan (MK-2400) in People With Small Cell Lung Cancer (MK-6070-003) (clinicaltrials.gov) - P1/2 | N=170 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

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

A phase Ib/II study of gocatamig (MK-6070; HPN328) and ifinatamab deruxtecan for relapsed/refractory extensive-stage small cell lung cancer (ES-SCLC) (ESMO 2025) - P1/2 | "Secondary objectives are to evaluate duration of response and progression-free survival by investigator assessment per RECIST v1.1 (part 1) and to characterize the pharmacokinetics and immunogenicity of gocatamig plus I-DXd combination therapy (part 1), I-DXd monotherapy (part 1), and gocatamig monotherapy (part 2). The 6070-002 study will enroll participants in Australia, Chile, China, Israel, Japan, South Korea, Spain, Türkiye, the United States of America, and other sites as the expansion gets underway."

P1/2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

Progress Continues in Multiple Cancers Across the DXd ADC Portfolio of Daiichi Sankyo (Businesswire) - "Data from...TROPION-PanTumor03, DESTINY-Gastric04, DESTINY-CRC02, DESTINY-PanTumor02 and DS-3939 – further support the strength of the DXd ADC portfolio of Daiichi Sankyo across multiple types of cancer....Updates of progress in lung cancer include a mini oral session reporting updated results from a phase 1/2 trial of gocatamig (2758MO), a DLL3 targeting T-cell engager being jointly developed by Merck, in patients with small cell lung cancer and other neuroendocrine cancers, as well as a poster presentation that will highlight the initial safety results from a phase 1b trial of valemetostat (2023P)..."

Clinical data • Colorectal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Lung Non-Squamous Non-Small Cell Cancer • Neuroendocrine Tumor • Small Cell Lung Cancer • Urothelial Cancer • HER-2

Preclinical Activity of the DLL3-Targeted T-cell Engager MK-6070 in Neuroendocrine Prostate Cancer. (PubMed, Mol Cancer Ther) - P1/2 | "MK-6070 also demonstrates antitumor activity in mixed tumors, affecting DLL3-negative prostate cancer cells after engagement with surrounding DLL3-expressing tumor cells, supporting a potential bystander effect. Overall, these data demonstrate the promising activity of MK-6070 in NEPC preclinical models including heterogeneous tumors, supporting the clinical development of MK-6070."

Journal • Preclinical • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • DLL3

Updated results from a phase I/II study of gocatamig for small cell lung cancer (SCLC) and other neuroendocrine cancers (ESMO 2025) - P1/2 | "There were no new or unexpected safety findings as of this data cutoff. Investigations of gocatamig at other monotherapy dosing schedules and in combination with other cancer therapies are ongoing."

P1/2 data • Endocrine Cancer • Genito-urinary Cancer • Lung Cancer • Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3

Trials-in-Progress Across Daiichi Sankyo’s Oncology Portfolio (Businesswire) - "A trial-in-progress poster will highlight the design of the DESTINY-Endometrial01 phase 3 trial...Three phase 2 trials-in-progress will include the HERTHENA-Breast03 trial (463eTiP)...the REJOICE-GI01 trial (1001TiP)...and, the KEYMAKER-U01 sub-studies 01H/01I (2081eTiP) evaluating ifinatamab deruxtecan, raludotatug deruxtecan or docetaxel in patients with stage IV NSCLC...The design of two additional early phase trials will be shared, including the phase 1/2 trial (2792TiP) evaluating ifinatamab deruxtecan and gocatamig in patients with relapsed/refractory ES-SCLC and a phase 1b trial (977P) of valemetostat..."

pMMR • Trial status • Biliary Tract Cancer • Endometrial Cancer • Gastroesophageal Junction Adenocarcinoma • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Pancreatic Ductal Adenocarcinoma • Prostate Cancer • Renal Cell Carcinoma • Triple Negative Breast Cancer • Urothelial Cancer

Preclinical activity of the DLL3-targeted T cell engager MK-6070 in neuroendocrine prostate cancer. (PubMed, Mol Cancer Ther) - P1/2 | "MK-6070 also demonstrates anti-tumor activity in mixed tumors, impacting DLL3-negative prostate cancer cells after engagement with surrounding DLL3-expressing tumor cells, supporting a potential bystander effect. Overall, these data demonstrate promising activity of MK-6070 in NEPC preclinical models including heterogeneous tumors, supporting the clinical development of MK-6070."

Journal • Preclinical • Genito-urinary Cancer • Genitourinary Neuroendocrine Carcinoma • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • DLL3

A Phase 1b/2 Study of Gocatamig and Ifinatamab Deruxtecan for Relapsed or Refractory Extensive-Stage Small Cell Lung Cancer (IASLC-WCLC 2025) - P1/2 | "Secondary objectives are to evaluate duration of response and progression-free survival per RECIST v1.1 (part 1) and to characterize the pharmacokinetics and immunogenicity of gocatamig plus I-DXd combination therapy (part 1), I-DXd monotherapy (part 1), and gocatamig monotherapy (part 2). The 6070-002 study will enroll participants in Australia, Chile, China, Israel, Japan, the Republic of Korea, Spain, Türkiye, and the United States of America."

P1/2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276 • DLL3

A Study to Evaluate the Safety and Efficacy of Gocatamig (MK-6070) and Ifinatamab Deruxtecan (I-DXd) in Participants With Relapsed/Refractory Extensive-Stage Small Cell Lung Cancer (MK-6070-002) (clinicaltrials.gov) - P1/2 | N=242 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | N=138 ➔ 242

Enrollment change • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Harnessing delta-like ligand 3: bridging biomarker discovery to next-generation immunotherapies in refractory small cell lung cancer. (PubMed, Front Immunol) - "The 2024 FDA approval of tarlatamab-a bispecific T-cell engager (BiTE) targeting DLL3 and CD3-marks a pivotal advancement, demonstrating improvement in survival in refractory disease. This review examines three key advances reshaping SCLC management: (1) mechanistic links between DLL3-driven tumorigenesis and PD-L1-mediated immunosuppression, (2) clinical progress in antibody-drug conjugates (ADCs) with next-generation payloads (e.g., FZ-AD005), multispecific BiTEs (e.g., HPN328), and engineered CAR-T/NK cells with enhanced metabolic resilience, and (3) precision strategies combining liquid biopsy for dynamic DLL3 profiling with immuno-PET imaging using [89Zr]Zr-DFO-SC16. Emerging synergies, such as combining DLL3-targeted BiTEs with ICIs to amplify T-cell infiltration or reprogramming CAR-T mitochondrial metabolism, further underscore the potential of multimodal approaches. Together, these developments signal a transformative era in SCLC treatment, where molecular..."

Biomarker • IO biomarker • Journal • Review • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3 • PD-L1

A Study to Evaluate the Safety and Efficacy of Gocatamig (MK-6070) and Ifinatamab Deruxtecan (I-DXd) in Participants With Relapsed/Refractory Extensive-Stage Small Cell Lung Cancer (MK-6070-002) (clinicaltrials.gov) - P1/2 | N=138 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2028 ➔ Aug 2029 | Trial primary completion date: Oct 2028 ➔ Aug 2029

Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Study in Participants With Advanced Cancers Associated With Expression of DLL3 (MK-6070-001/HPN328-4001) (clinicaltrials.gov) - P1/2 | N=232 | Recruiting | Sponsor: Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | Trial completion date: Jun 2027 ➔ Nov 2027 | Trial primary completion date: Jun 2027 ➔ Nov 2027

Trial completion date • Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

A Study in Participants With Advanced Cancers Associated With Expression of DLL3 (MK-6070-001/HPN328-4001) (clinicaltrials.gov) - P1/2 | N=232 | Recruiting | Sponsor: Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | Trial completion date: Feb 2026 ➔ Jun 2027 | Trial primary completion date: Feb 2026 ➔ Jun 2027

Monotherapy • Trial completion date • Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

A Study to Evaluate the Safety and Efficacy of Gocatamig (MK-6070) and Ifinatamab Deruxtecan (I-DXd) in Participants With Relapsed/Refractory Extensive-Stage Small Cell Lung Cancer (MK-6070-002) (clinicaltrials.gov) - P1/2 | N=138 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

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

A Study to Evaluate the Safety and Efficacy of MK-6070 and Ifinatamab Deruxtecan (I-DXd) in Participants With Relapsed/Refractory Extensive-Stage Small Cell Lung Cancer (MK-6070-002) (clinicaltrials.gov) - P1/2 | N=138 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

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

A phase 1/2 trial in progress of MK-6070 (aka HPN328), a DLL3-targeting T cell engager, as monotherapy or combination therapy for advanced cancers associated with DLL3 expression (SITC 2024) - P1/2 | "Enrollment and evaluation of target dose levels and schedules is ongoing in SCLC-specific combination cohorts of MK-6070 IV Q2W with atezolizumab IV Q4W. Cohorts combining the B7 homolog 3 ADC, ifinatamab deruxtecan, with MK-6070 will be enrolling to determine safety and preliminary efficacy in SCLC. Clinical trial information: NCT04471727."

Combination therapy • IO biomarker • Metastases • Monotherapy • P1/2 data • Endocrine Cancer • Genito-urinary Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • CD276 • DLL3

Impact of Brain Metastases on Safety and Efficacy of MK-6070, a DLL3-Targeting T Cell Engager, in Small Cell Lung Cancer (IASLC-WCLC 2024) - P1/2 | "Introduction : MK-6070 (aka HPN328) is a DLL3-targeting T cell engager being studied in an ongoing phase 1/2 trial in patients (pts) with high grade neuroendocrine tumors associated with DLL3 expression, including small cell lung cancer (SCLC)...This trial is ongoing and data continue to mature. Updated safety and efficacy data including duration of response will be presented."

Clinical • IO biomarker • Brain Cancer • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

A Study in Participants With Advanced Cancers Associated With Expression of DLL3 (MK-6070-001/HPN328-4001) (clinicaltrials.gov) - P1/2 | N=232 | Recruiting | Sponsor: Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) | N=162 ➔ 232 | Trial primary completion date: Jul 2025 ➔ Jan 2026

Enrollment change • Metastases • Monotherapy • Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3

Daiichi Sankyo and Merck & Co., Inc., Rahway, NJ, USA Enter into Global Development and Commercialization Agreement for MK-6070 (Daiichi Sankyo Press Release) - "Daiichi Sankyo...and Merck & Co., Inc...have expanded their existing global co development and co-commercialization agreement for three investigational DXd antibody drug conjugates to include Merck & Co., Inc., Rahway, NJ, USA’s MK-6070, an investigational delta-like ligand 3 (DLL3) targeting T-cell engager. The companies will jointly develop and commercialize MK-6070 worldwide, except in Japan where Merck & Co., Inc., Rahway, NJ, USA will maintain exclusive rights. Merck & Co., Inc., Rahway, NJ, USA will be solely responsible for manufacturing and supply for MK-6070.....Under the terms of the agreement, Merck & Co., Inc., Rahway, NJ, USA will receive an upfront cash payment of $170 million and has also satisfied a contingent quid obligation from the original collaboration agreement."

Licensing / partnership • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

Updated results from a phase 1/2 study of HPN328, a tri-specific, half-life (T1/2) extended DLL3-targeting T-cell engager in patients (pts) with small cell lung cancer (SCLC) and other neuroendocrine cancers (NEC). (ASCO 2024) - P1/2 | "HPN328 is well tolerated and clinically active in SCLC, NEC, and NEPC. Current dose optimization cohorts have completed enrollment and data continue to mature; selection of a recommended phase 2 dose will be made based upon complete mature data. Updated safety and efficacy results will be presented."

Clinical • IO biomarker • P1/2 data • Trispecific • Endocrine Cancer • Fatigue • Genito-urinary Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3

Study in Patients With Advanced Cancers Associated With Expression of DLL3 (clinicaltrials.gov) - P1/2 | N=162 | Recruiting | Sponsor: Harpoon Therapeutics | Trial completion date: Jun 2024 ➔ Dec 2025 | Trial primary completion date: Jan 2024 ➔ Jul 2025

IO biomarker • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • DLL3

HPN328, a Trispecific T Cell-activating Protein Construct Targeting DLL3-Expressing Solid Tumors. (PubMed, Mol Cancer Ther) - "Preclinical and nonclinical characterization suggests that HPN328 is a highly efficacious, safe, and novel therapeutic candidate. A phase 1/2 clinical trial is currently underway testing safety and efficacy in patients with DLL3 expressing malignancies."

Journal • Trispecific • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3

Merck Completes Acquisition of Harpoon Therapeutics, Inc. (Merck (MSD) Press Release) - "Merck...announced the completion of the acquisition of Harpoon Therapeutics, Inc...Harpoon’s common stock will no longer be publicly traded or listed on the Nasdaq Stock Market...Harpoon’s lead candidate, MK-6070 (formerly known as HPN328), is a T-cell engager targeting delta-like ligand 3 (DLL3), an inhibitory canonical Notch ligand that is expressed at high levels in small cell lung cancer (SCLC) and neuroendocrine tumors...Additional pipeline candidates include HPN217, a T-cell engager targeting B-cell maturation antigen (BCMA), currently in Phase 1 clinical development for the treatment of patients with relapsed/refractory multiple myeloma, and several preclinical stage candidates, including HPN601...Merck is recording a non-tax deductible charge to R&D expense of approximately $650 million."

M&A • Multiple Myeloma • Neuroendocrine Tumor • Small Cell Lung Cancer • Solid Tumor

HPN328 Shows Clinical Activity and Tolerability in Neuroendocrine Prostate Cancer (OncLive) - P1/2 | N=162 | NCT04471727 | Sponsor: Harpoon Therapeutics | "When HPN328 was administered at a priming dose of 2 mg, two dose-limiting toxicities (DLTs) were observed. The priming dose was then de-escalated to 1 mg. At the target doses, no DLTs were reported, and the maximum tolerated dose (MTD) was not yet reached. Adverse effects (AEs) were determined to be manageable, with cytokine release syndrome (CRS) occurring with the first dose of the agent. Most of the CRS events were grade 1 or 2 in severity....In all response-evaluable patients treated with the 1-mg priming dose of the agent (n = 50), the overall response rate (ORR) was 56%."

Cytokine release syndrome • P1/2 data • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor

ASCOGU24: Himisha Beltran, MD | Dana-Farber Cancer Institute (YouTube) - "#ASCOGU24: Interim phase 1 results show HPN328, a T-cell engager, is well tolerated and clinically active for patients across a wide range of neuroendocrine carcinomas. Dana-Farber's Himisha Beltran, MD explains more here."

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