Study Launches Exploring Peluntamig Combo in DLL3-Expressing Tumors

This article originally appeared on OncLive^®.

Dosing has started in a clinical evaluating peluntamig, which targets DLL3 and CD47, combined with chemotherapy in patients with DLL3-expressing cancers.

Image credit: Crystal light-stock.adobe.com

A clinical trial evaluating peluntamig (PT217) with chemotherapy for the treatment of small cell lung cancer (SCLC) and neuroendocrine carcinoma (NEC) has dosed its first patient.¹

Peluntamig is a first-in-class native IgG-like bispecific antibody that targets DLL3 and CD47. The agent is currently being developed as a potential treatment for patients with SCLC and NEC, including neuroendocrine prostate cancer (NEPC).

The FDA has already granted peluntamig 2 orphan drug designations for the treatment of SCLC and NEC, as well as 2 fast track designations for the treatment of extensive-stage small cell lung cancer (ES-SCLC) with disease progression following treatment with platinum chemotherapy with or without a checkpoint inhibitor, and metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC), respectively.

Last year, Phanes Therapeutics, Inc., the drug developer, entered into a clinical supply agreement with Roche to study the combination of peluntamig and the anti–PD-L1 therapy atezolizumab (Tecentriq).

The phase 1/2, multicenter SKYBRIDGE trial (NCT05652686) is currently investigating peluntamig’s safety, tolerability, pharmacokinetics, and preliminary efficacy in patients with advanced or refractory cancers expressing DLL3.² The study is recruiting patients across sites in Colorado, Massachusetts, North Carolina, Oklahoma, Texas, and Virginia.

Enrollment is open to patients with measurable disease by RECIST v1.1, an ECOG performance status of 0 or 1, adequate organ function, resolution of adverse events from prior therapies, and a life expectancy of at least 3 months. Patients who are pregnant or lactating, have autoimmune disease, have a known concurrent malignancy, or have uncontrolled hypertension are not eligible for enrollment in the study.

The study consists of dose-escalation and dose-expansion phases. The dose-escalation phase aims to establish the recommended phase 2 dose (RP2D), and the dose-expansion phase will include 2 cohorts. One cohort will receive the RP2D, and the other will receive 1 dose level lower.

The primary end points of the study are to evaluate dose-limiting toxicities, the maximum tolerated dose, the RP2D, and safety. Secondary end points include preliminary efficacy and pharmacokinetics. Disease control rate is an additional exploratory end point.

With an estimated enrollment of 52 patients, the trial has an anticipated completion date of June 2025.

Additionally, a phase 1 trial of peluntamig is ongoing in China (CTR20242720).¹

REFERENCES

1. Phanes Therapeutics announces first patient dosed in clinical study of peluntamig (PT217) in combination with chemotherapy. News release. Phanes Therapeutics, Inc. February 19, 2025. Accessed February 20, 2025. https://tinyurl.com/2f336uuc
2. A phase 1 study of PT217 in patients with advanced refractory cancers expressing DLL3 (the SKYBRIDGE study). ClinicalTrials.gov. Updated January 31, 2025. Accessed February 20, 2025. https://clinicaltrials.gov/study/NCT05652686