A Study of Peluntamig (PT217) in Patients With Neuroendocrine Carcinomas Expressing DLL3 (the SKYBRIDGE Study)

September 18, 2025 updated by: Phanes Therapeutics

An Open-label, Multicenter, Dose Escalation, and Dose Expansion Phase 1/2 Study With Peluntamig (PT217) Followed by a Key ChemotherapY and/or Checkpoint Inhibitor ComBination in Patients With NeuRoendocrIne Carcinomas That Are Known to be DLL3 expressinG CancErs (SKYBRIDGE)

This is a first-in-human, Phase 1/2, open-label, dose escalation, dose expansion and combination study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of Peluntamig (PT217) as a monotherapy and in combination with chemotherapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

203

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
    • Colorado
      • Denver, Colorado, United States, 80218
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Sidney Kimmel Comprehensive Cancer Center at John Hopkins
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
          • Phone Number: 617-724-4000
        • Principal Investigator:
          • Catherine Meador, MD, PhD
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Principal Investigator:
          • Jacob Sands, MD
        • Contact:
    • Missouri
      • St Louis, Missouri, United States, 63108
        • Recruiting
        • Washington University School of Medicine (Siteman Cancer Center)
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina at Chapel Hill
        • Principal Investigator:
          • Jared Weiss, MD
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • Sarah Cannon Research Institute University of Oklahoma
        • Principal Investigator:
          • Abdul Naqash, MD
        • Contact:
    • Oregon
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Providence Portland Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • Not yet recruiting
        • The University of Texas, MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • Mays Cancer Center / University of Texas, San Antonio
        • Principal Investigator:
          • Daruka Mahadevan, MD, PhD
        • Contact:
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • NEXT Virginia
        • Principal Investigator:
          • Alexander Spira, MD, PhD, FACP
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria

  1. NECs that have transformed from NSCLC are not eligible. Part A: Patients with histologically or cytologically confirmed unresectable advanced or metastatic small cell lung cancer (SCLC), large cell neuroendocrine carcinoma of the lung (LCNEC), or extrapulmonary neuroendocrine carcinoma (EP-NEC). Patients with tumors that are of mixed histology are eligible only if neuroendocrine carcinoma/small cell cancer component is predominant and represents at least 50% of the overall tumor tissue. Patients with well differentiated grade 3 neuroendocrine tumors (Ki-67 ≥ 55%) may be considered if their tumors are DLL3 positive.

    Patients may have progressed after standard of care treatments (at least one line of platinum-based chemotherapy with or without immune checkpoint inhibitor for SCLC patients) or other treatment options, or for whom treatment is not available or not tolerated.

    Part B: Patients must meet the same criteria in Part A, C or D.

    Part C:

    • Cohort C1: patients with LCNEC or EP-NEC eligible for first-line (1L) CE treatment. SCLC patients who have relapsed on a 1L treatment (including platinum-based therapy with or without ICI) but remain platinum sensitive (defined as patients who experienced disease progression at least 90 days after their last platinum based chemotherapy) and are eligible for CE treatment rechallenge.

    Cohort C2: patients with SCLC, LCNEC and EP-NEC eligible for second line (2L) paclitaxel treatment.

    Part D:

    • Cohort D1: will include 2L patients with SCLC, LCNEC, pr EP-NEC that have progressed/relapsed from their first-line treatment that may have included an ICI.
    • Cohort D2: will include 1L ES-SCLC patients that have completed their induction therapy with carboplatin and etoposide plus atezolizumab and are eligible to continue with atezolizumab. These patients must have either stable disease or partial response prior to enrollment.
    • Cohort D3: will include 1L ES-SCLC patients that are treatment naïve or have received C1D1/2/3 and are eligible for treatment with CE plus atezolizumab.
  2. Able to provide a formalin fixed, paraffin embedded (FFPE) tumor tissue sample (preferably a newly acquired biopsy, or if not possible, archival tissue) to be assessed for DLL3 expression and other biomarkers.
  3. ECOG performance status of 0 or 1.
  4. Adequate organ function confirmed at screening and within 72 hours of initiating C1D1 of Peluntamig (PT217) treatment.

Key Exclusion Criteria

  1. Women who are pregnant or lactating.
  2. Women of child-bearing potential (WOCBP) who do not use adequate birth control.
  3. Autoimmune disease requiring systemic treatment within the past twelve months.
  4. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2, and excluding ICIs) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment with Peluntamig (PT217).
  5. Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications (≥ 10 mg prednisone, or equivalent) within 14 days prior to study drug Peluntamig (PT217), or anticipation of need for systemic immunosuppressive medication during study drug Peluntamig (PT217).
  6. Patients who have experienced Grade ≥ 3 immune-related events, such as (non-infectious) pneumonitis, interstitial lung disease, myocarditis.
  7. Treatment with therapeutic oral or i.v. antibiotics within 2 weeks prior to initiation of study treatment with Peluntamig (PT217).

  8. Patients with untreated brain or central nervous system (CNS) metastases or brain/CNS metastases that have progressed.

    Note: Patients with treated brain metastases that are off corticosteroids and have been clinically stable for 14 days are eligible for treatment.

  9. Impaired cardiac function or significant diseases.
  10. For Part D only, uncontrolled hypercalcemia.
  11. For Part D only, significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina.
  12. Prior hemolytic anemia or Evans Syndrome in the last 3 months.
  13. Patients who have Grade ≥ 3 neuropathy.
  14. Patients who are currently receiving treatment with therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants .

Additional criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A: Dose Escalation
A standard 3+3 dose escalation design will be employed.
Drug: Peluntamig (PT217)
A bispecific antibody (bsAb) against DLL3 and CD47.
Experimental: Part B: Dose Expansion
Part B cohorts will open after the dose level considered for RDE has been cleared in Parts A, C and D.
Drug: Peluntamig (PT217)
A bispecific antibody (bsAb) against DLL3 and CD47.
Experimental: Part C: Chemotherapy Combination Therapy
Part C of the study will include Cohorts C1 and C2, combining Peluntamig (PT217) with chemotherapy.
Drug: Carboplatin + Etoposide
Administered per Standard of Care.
Drug: Paclitaxel.
Administered per Standard of Care.
Drug: Peluntamig (PT217)
A bispecific antibody (bsAb) against DLL3 and CD47.
Experimental: Part D: ICI Combination Therapy
In part D, Peluntamig (PT217) will be given in combination with atezolizumab, either alone or in combination with chemotherapy.
Drug: Carboplatin + Etoposide
Administered per Standard of Care.
Drug: Atezolizumab
Administered per Standard of Care.
Drug: Peluntamig (PT217)
A bispecific antibody (bsAb) against DLL3 and CD47.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine the dose-limiting toxicity (DLT) of Peluntamig (PT217).
Time Frame: Through study completion.
Through study completion.
To determine the maximum tolerated dose (MTD) of Peluntamig (PT217) if reached.
Time Frame: Through study completion.
Through study completion.
To determine recommended dose for expansion (RDE) of Peluntamig (PT217).
Time Frame: Through study completion.
Through study completion.
To evaluate the safety and tolerability of Peluntamig (PT217).
Time Frame: Through study completion.
Through study completion.
To evaluate the efficacy of Peluntamig (PT217) monotherapy or in combination treatments
Time Frame: Through study completion
Through study completion

Secondary Outcome Measures

Outcome Measure
Time Frame
To evaluate the pharmacokinetics of Peluntamig (PT217).
Time Frame: Through study completion.
Through study completion.
To evaluate the immunogenicity (ADA) of Peluntamig (PT217).
Time Frame: Through study completion.
Through study completion.
To further evaluate the efficacy of Peluntamig (PT217) monotherapy or in combination treatments
Time Frame: Through study completion.
Through study completion.

Other Outcome Measures

Outcome Measure
Time Frame
To evaluate pharmacodynamic markers of PT217 biological activity
Time Frame: Through study completion, an average of 2 years.
Through study completion, an average of 2 years.
To evaluate pretreatment DLL3 expression in correlation with primary endpoints by immunohistochemistry.
Time Frame: Through study completion, an average of 2 years.
Through study completion, an average of 2 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Phanes Therapeutics

Collaborators

Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 5, 2023

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

August 1, 2028

Study Registration Dates

First Submitted

December 7, 2022

First Submitted That Met QC Criteria

December 7, 2022

First Posted (Actual)

December 15, 2022

Study Record Updates

Last Update Posted (Estimated)

September 23, 2025

Last Update Submitted That Met QC Criteria

September 18, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PT217X1101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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