Gocatamig

Shows activity

Also known as:

HPN328 MK-6070 DS-3280

Cancer types include:

prostate cancer small cell lung cancer

TrialFetch AI Analysis

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Overview

Gocatamig (also known as HPN328; MK-6070; DS-3280) is an investigational, trispecific T‑cell engager being developed for DLL3‑expressing malignancies, particularly small cell lung cancer (SCLC) and other neuroendocrine cancers. As of 2024–2025, it is in an ongoing phase 1/2 study as monotherapy and in combinations, with reported early signs of antitumor activity. Daiichi Sankyo and Merck (MSD) announced a global co‑development/co‑commercialization agreement for MK‑6070 in August 2024 (Japan rights retained by MSD). Gocatamig has received FDA Orphan Drug Designation for SCLC. (cdek.pharmacy.purdue.edu)

Mechanism of action

Target: Delta‑like ligand 3 (DLL3), aberrantly expressed on many neuroendocrine tumors (e.g., SCLC, neuroendocrine prostate cancer), with minimal expression in normal tissues. (msd.com)
Modality: “TriTAC” construct with three binding domains: anti‑DLL3 for tumor engagement, anti‑CD3 for T‑cell recruitment/activation, and anti‑albumin for half‑life extension. Preclinical studies demonstrate potent DLL3‑dependent cytotoxicity, T‑cell activation, and long serum half‑life supporting weekly or less‑frequent dosing; evidence of long‑term antitumor immunity in murine models has been reported. (aacrjournals.org)

Efficacy

Phase 1/2, dose‑escalation/optimization monotherapy (NCT04471727; cutoff Jan 5, 2024): - Overall response rate (confirmed) in SCLC: 50% (12/24), including 1 complete response, in dose‑optimization cohorts using a 1‑mg priming dose and 12–24 mg target dose administered weekly or every 2 weeks.
- Confirmed ORR in non‑prostate neuroendocrine carcinomas: 44% (4/9), including 1 complete response.
- In NEPC, several unconfirmed partial responses were noted; some patients remained on treatment >20 weeks.
These results are preliminary and from an ongoing study; RP2D selection pending. (ascopubs.org)

Earlier interim datasets from the same trial (2022–2024) showed tumor shrinkage and preliminary responses across DLL3‑expressing tumors, supporting continued development and subsequent dose‑optimization cohorts. (ascopubs.org)

Combination cohorts: The ongoing trial includes gocatamig with atezolizumab and with ifinatamab deruxtecan (I‑DXd, DS‑7300/MK‑2400); first SCLC patients in the atezolizumab combination were dosed in September 2023. Mature efficacy data for combinations have not yet been reported publicly. (cdek.pharmacy.purdue.edu)

Safety

Across 86 treated patients (all doses; data cutoff Jan 5, 2024): - Common treatment‑related adverse events (≥10%): cytokine release syndrome (CRS) 59% (Grade 1: 30%, Grade 2: 26%, Grade ≥3: 3% overall; no Grade 3–4 CRS at target doses), dysgeusia 36%, fatigue 34%, diarrhea 19%, nausea 17%, vomiting 14%, decreased appetite 13%, neutropenia 13%, weight decreased 11%.
- Immune effector cell‑associated neurotoxicity syndrome (ICANS): 9%, all Grade 1–2.
- Dosing strategy: step‑up priming (max tolerated priming dose 1 mg) with weekly or every‑2‑week target dosing up to 24 mg; maximum tolerated target dose was not reached by cutoff.
- Pharmacokinetics: median half‑life ~71 hours; linear, dose‑proportional exposure.
CRS events were most frequent after the initial priming dose and were uncommon with subsequent doses. (ascopubs.org)

Trial landscape

Ongoing first‑in‑human phase 1/2 (NCT04471727): gocatamig monotherapy and combinations with atezolizumab or I‑DXd in DLL3‑expressing cancers; primary completion currently estimated November 2027. (fdaaa.trialstracker.net)

Active trials using Gocatamig

Found 2 active trials using this drug:

A Phase 1b/2 Open-Label Clinical 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

Sponsor: Merck Sharp & Dohme LLC (industry) Phase: 1/2 Start date: Feb. 27, 2025

TrialFetch AI summary: Adults with relapsed/refractory extensive-stage SCLC after ≥1 prior systemic therapy (including platinum) receive gocatamig (HPN328; trispecific DLL3×CD3 T‑cell engager with albumin-binding for half-life) as monotherapy or combined with ifinatamab deruxtecan (B7‑H3–targeted DXd ADC) or with durvalumab (PD‑L1 inhibitor). Key exclusions include uncontrolled effusions, significant/suspected ILD/pneumonitis, major cardiopulmonary disease/events, uncontrolled brain mets, active infections/viral hepatitis, and recent chemo/radiation; archival or fresh tumor tissue required.

ClinicalTrials.gov ID: NCT06780137

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).

Sponsor: Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) (industry) Phase: 1/2 Start date: Dec. 14, 2020

TrialFetch AI summary: Adults with DLL3-expressing advanced neuroendocrine cancers—including relapsed/refractory SCLC after platinum, treatment-emergent or de novo neuroendocrine prostate cancer, and other high-grade NETs lacking effective options—receive gocatamig (HPN328), a trispecific T-cell engager targeting DLL3/CD3 with albumin-binding for half-life, as IV monotherapy on varied schedules or in combination with atezolizumab (PD-L1 inhibitor) or ifinatamab deruxtecan (B7-H3 ADC). Key exclusions include active/untreated CNS disease, significant autoimmune/immunosuppression, recent major cardiovascular events, uncontrolled viral infections, and interstitial lung disease.

ClinicalTrials.gov ID: NCT04471727