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

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."

Video

Interim 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 neuroendocrine prostate cancer (NEPC) and other neuroendocrine neoplasms (NEN). (ASCO-GU 2024) - P1/2 | "HPN328 is well tolerated and clinically active. MTD determination, dose escalation, and dose optimization are ongoing. Updated safety and efficacy results including recently enrolled NEPC and SCBC pts will be presented."

Clinical • P1/2 data • Trispecific • Bladder Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • DLL3

Merck to Acquire Harpoon Therapeutics, Further Diversifying Oncology Pipeline (Businesswire) - "Merck...and Harpoon Therapeutics, Inc...today announced that the companies have entered into a definitive agreement under which Merck, through a subsidiary, will acquire Harpoon for $23.00 per share in cash for an approximate total equity value of $680 million...'We look forward to further evaluating HPN328 in innovative combinations with other pipeline candidates.'...Additional pipeline candidates include HPN217 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, a conditionally activated targeting epithelial cell adhesion molecule (EpCAM) for the treatment of certain patients with EpCAM expressing tumors....The transaction is expected to close in the first half of 2024 and will be accounted for as an asset acquisition."

M&A • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Oncology • Small Cell Lung Cancer • Solid Tumor

Harpoon Therapeutics Abstract for HPN328 Accepted for Rapid Oral Presentation at the 2024 American Society of Clinical Oncology Genitourinary Cancers Symposium (GlobeNewswire) - "Harpoon Therapeutics, Inc...today announced abstract acceptance and an upcoming rapid oral presentation of updated interim monotherapy data from its Phase 1/2 clinical trial evaluating HPN328 in small cell lung cancer (SCLC) and other neuroendocrine tumor types at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO-GU) being held in San Francisco, CA and virtually on January 25-27, 2024. HPN328 targets delta-like ligand 3 (DLL3) and is derived from Harpoon’s proprietary Tri-specific T cell Activating Construct (TriTAC^®) platform designed to recruit a patient’s own immune cells to kill tumor cells."

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

Interim results from a phase I/II 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 neoplasms (NEN) (ESMO 2023) - P1/2 | "Future planned cohorts include every other week dosing and HPN328 + atezolizumab. Updated safety and efficacy results including pts recently enrolled in backfill cohorts will be presented."

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

Harpoon Therapeutics Shares Rise 39% After Positive HPN328 Trial Data (Firstwordpharma Press Release) - "Shares of Harpoon Therapeutics surged 39% in premarket trading Monday after the company said it saw positive results in its Phase I/II clinical trial evaluating HPN328 in small cell lung cancer and other neuroendocrine tumour types...The drug was found to be generally well tolerated across all dose cohorts, with treatment-related adverse events occurring in 67 patients....The drugmaker plans to identify the recommended Phase II regimen in the monotherapy setting by the end of the year and potentially begin registrational studies in multiple tumour types in 2024."

New trial • P1 data • Stock price • Neuroendocrine Tumor • Small Cell Lung Cancer

Harpoon Therapeutics Announces Updated Interim Tolerability and Response Data from Phase 1/2 Clinical Trial of T Cell Engager HPN328 at ESMO Congress 2023 (GlobeNewswire) - P1/2 | N=162 | NCT04471727 | Sponsor: Harpoon Therapeutics | "Harpoon Therapeutics...announced the updated interim monotherapy data from its Phase 1/2 clinical trial evaluating HPN328 in small cell lung cancer (SCLC) and other neuroendocrine tumor types in a poster at the European Society of Medical Oncology Congress (ESMO) 2023....HPN328 was generally well tolerated across all dose cohorts (N=71). Treatment-related adverse events (TRAEs) occurred in 67 patients (94%)....The preliminary response data for evaluable patients treated in 1 mg priming dose cohorts showed confirmed response rate of 35% (11/31) across all tumor types. In SCLC, the confirmed response rate was 32% (6/19) with one confirmed complete response....Enrollment in monotherapy dose cohorts nearing completion, on track to select Phase 2 dose(s) by end of 2023."

P1/2 data • Trial status • Neuroendocrine Tumor • Small Cell Lung Cancer

Harpoon Therapeutics to Host Webcast Reviewing HPN328 Interim Data Presented at ESMO Congress 2023 on October 23, 2023 (GlobeNewswire) - "During the call, management will provide an in-depth review of the HPN328 interim data presented that day at ESMO Congress 2023. Harpoon will present data from over 70 patients across multiple DLL3 expressing tumor types in HPN328 monotherapy cohorts, with an emphasis on the ongoing 1 mg priming cohorts with target doses up to 24 mg. Full enrollment of these 1 mg priming dose cohorts will be the basis for selecting the recommended Phase 2 dose(s) by the end of this year. The ESMO poster will share tolerability data from all enrolled patients and preliminary response data in patients at doses above the efficacious threshold of 1.215 mg."

Enrollment status • P1/2 data • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor

Harpoon Therapeutics to Present Interim Tolerability and Response Data from Phase 1/2 Clinical Trial of T Cell Engager HPN328 at ESMO Congress 2023 (GlobeNewswire) - ":Harpoon Therapeutics, Inc...today announced that it will present interim monotherapy data from its Phase 1/2 clinical trial evaluating HPN328 in small cell lung cancer (SCLC) and other neuroendocrine neoplasms (NEN) in a poster presentation at the European Society of Medical Oncology Congress (ESMO) 2023 taking place in Madrid, Spain from October 20-24, 2023....In our poster, we will share tolerability data from all enrolled patients and preliminary response data in patients at doses above the efficacy threshold of 1.215 mg,'..."

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

Harpoon Therapeutics Announces First Patients with Small Cell Lung Cancer Dosed in HPN328 Combination Cohort (GlobeNewswire) - "Harpoon Therapeutics, Inc...announced dosing of the first patients with small cell lung cancer (SCLC) in an ongoing Phase 1/2 trial of HPN328, a DLL3 targeting TriTAC^®, in combination with atezolizumab (Tecentriq^®)....Enrollment in the combination cohorts has been initiated at the 12 mg Q2W HPN328 dose level, and escalation is planned per protocol dependent on data, with initial results from these combination cohorts expected in 2024. Separately, HPN328 interim Phase 1 monotherapy data will be presented at the European Society for Medical Oncology (ESMO) held on October 20-24, 2023."

P1/2 data • Trial status • Lung Cancer • Oncology • Small Cell Lung Cancer

Harpoon Therapeutics to Host KOL Event in Person and via Webcast on September 15, 2023 (GlobeNewswire) - "Harpoon Therapeutics, Inc...announced that management will host an in-person event 'DLL3 Market Opportunity and KOL Discussion of HPN328', in New York on September 15, 2023 from 8:00 to 9:30 a.m. ET. Invited key opinion leaders (KOLs) will discuss HPN328, a DLL3-targeting tri-specific T cell engager, and its potential in the treatment of small cell lung cancer (SCLC), NEPC (neuroendocrine prostate cancer) and other neuroendocrine carcinomas. The agenda will also include a management overview of the market potential for selected DLL3 expressing tumor types and an update on Harpoon’s clinical development pipeline, including upcoming milestones."

Clinical data • Genito-urinary Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor

Harpoon Therapeutics Reports Second Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "HPN328 (DLL3) Phase 1/2 trial in small cell lung cancer (SCLC) and other neuroendocrine cancers: Abstract with interim data accepted for poster presentation at the European Society for Medical Oncology (ESMO) being held October 20-24, 2023 in Madrid; Enrollment in combination therapy of HPN328 with atezolizumab (Tecentriq®) in patients with SCLC, as part of the Phase 1/2 dose escalation trial, is anticipated to initiate in the third quarter of 2023; Completion of the Phase 1 monotherapy regimen exploration is expected in the second half of 2023, including the identification of the recommended Phase 2 regimen(s) in the monotherapy setting by the end of 2023."

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

Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer. (PubMed, J Hematol Oncol) - "First, we discuss the clinical experience with rovalpituzumab tesirine (Rova-T), a DLL3-targeting ADC, the development of which was halted due to a lack of efficacy in phase 3 studies, with a view to understanding the lessons that can be garnered for the rapidly evolving therapeutic landscape in SCLC. We then review preclinical and clinical data for several DLL3-targeting agents that are currently in development, including the TCE molecules-tarlatamab (formerly known as AMG 757), BI 764532, and HPN328-and the CAR T-cell therapy AMG 119. We conclude with a discussion of the future challenges and opportunities for DLL3-targeting therapies, including the utility of DLL3 as a biomarker for patient selection and disease progression, and the potential of rational combinatorial approaches that can enhance efficacy."

IO biomarker • Journal • Review • Endocrine Cancer • Lung Cancer • Neuroendocrine Tumor • Oncology • Small Cell Lung Cancer • Solid Tumor • DLL3