Investigating gocatamig for advanced cancers with DLL3 expression

A Phase 1/2 Open-label, Multicenter, Dose Escalation and Dose Expansion Study of the Safety, Tolerability, and Pharmacokinetics of HPN328 Monotherapy and HPN328 With Atezolizumab or Ifinatamab Deruxtecan (I-DXd) in Patients With Advanced Cancers Associated With Expression of Delta-like Canonical Notch Ligand 3 (DLL3).

Phase1; Phase2 Interventional Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) · NCT04471727

This study is testing a new treatment called gocatamig, alone and with other drugs, to see if it helps people with advanced cancers that have a specific protein called DLL3.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment232 (estimated)
Ages18 Years and up
SexAll
SponsorHarpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) Industry-sponsored
Drugs / interventionschemotherapy, radiation, methotrexate, cyclophosphamide, prednisone, Atezolizumab
Locations11 sites (Los Angeles, California and 10 other locations)
Trial IDNCT04471727 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, efficacy, and pharmacokinetics of gocatamig, both alone and in combination with Atezolizumab and Ifinatamab Deruxtecan (I-DXd), in patients with advanced cancers that express Delta-like Canonical Notch Ligand 3 (DLL3). It aims to determine the maximum tolerated dose and the recommended dose for expansion for these treatments. Participants include those with relapsed or refractory small-cell lung cancer and neuroendocrine tumors. The study will involve both Phase 1 and Phase 2 assessments to gather comprehensive data on treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates include individuals with relapsed or refractory small-cell lung cancer or neuroendocrine tumors that express DLL3.

Not a fit: Patients with cancers not associated with DLL3 expression or those who have not undergone prior systemic therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced cancers associated with DLL3 expression.

How similar studies have performed: Other studies targeting DLL3 have shown promise, indicating potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Has a histologically or cytologically confirmed malignancy associated with expression of Delta-like Canonical Notch Ligand 3 (DLL3)
* Has small cell lung cancer (SCLC) which is relapsed/refractory following at least 1 prior line of systemic therapy that included platinum-based chemotherapy
* Has Neuroendocrine Prostate Cancer (NEPC; de novo or treatment-emergent) which is relapsed/refractory to standard systemic therapy
* Has high-grade neuroendocrine tumor types other than SCLC and NEPC, with at least one of the following:

  * Disease that is relapsed/refractory to standard systemic therapy
  * Disease for which standard therapy does not exist
  * Disease for which standard therapy is not considered appropriate by the Investigator
* Must be able to provide archival tissue sample or fresh biopsy tissue sample

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Has untreated central nervous system (CNS) metastases
* Has a glioma or other primary CNS malignancy
* Has spinal cord compression or symptomatic/uncontrolled epidural disease
* Has a history of intracranial hemorrhage or spinal cord hemorrhage
* Has active neurologic paraneoplastic syndrome
* Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (e.g., biweekly or more frequently)
* Has active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis
* Is ongoing treatment with immunosuppressive medications (including, but not limited to, systemic corticosteroids \[prednisone dose \>10mg per day or equivalent\], cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[TNF\] alpha agents) within 2 weeks prior to initiation of treatment, or anticipation of need for systemic immunosuppressive medication during study treatment (except protocol-required pre-medications)
* Has a history of clinically significant cardiovascular disease such as myocardial infarction, symptomatic congestive heart failure (New York Heart Association \> class II), and/or uncontrolled cardiac arrhythmia within 6 months of the first dose of study drug
* Has a history of arterial thrombosis (e.g., stroke or transient ischemic attack) within 6 months
* Has active viral hepatitis, defined as hepatitis A (hepatitis A virus immunoglobulin M \[IgM\] positive), hepatitis B (hepatitis B virus surface antigen \[HbsAg\] positive), or hepatitis C (hepatitis C virus \[HCV\] antibody positive, confirmed by HCV ribonucleic acid). HCV with undetectable virus after treatment are eligible. Hepatitis B virus (HBV) with undetectable viral load by quantitative polymerase chain reaction (PCR) are eligible.
* Has uncontrolled infection with Human Immunodeficiency Virus (HIV)-1 or HIV-2. Well-controlled HIV are eligible.
* Has a history of allogeneic stem cell transplant or solid-organ transplant
* Has had treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
* Has a history of severe anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
* Has a history of interstitial lung disease, idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT). History of radiation pneumonitis in the radiation field is permitted
* Has had treatment with other investigational drug within 3 weeks of scheduled dosing (or 5 half-lives of drug, whichever is shorter)

Where this trial is running

Los Angeles, California and 10 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Small-Cell Lung CancerNeuroendocrine CarcinomaLung CancerDLL3HarpoonTriTACProstate CancerNeuroendocrine Tumors
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.