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

July 13, 2026 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)
      • Los Angeles, California, United States, 90033
        • Recruiting
        • USC Norris Comprehensive Cancer Center
    • Colorado
      • Denver, Colorado, United States, 80218
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University Cancer Center
    • 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:
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Medical Center
    • 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
      • 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:
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutch Cancer Center

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. 18 years or older and able to sign informed consent and comply with the protocol.
  2. Measurable disease as defined by RECIST v1.1 criteria for solid tumors.

  3. 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 eligibility criteria as patients in Part A, C or D.

    Part C:

    • Substudy 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.
    • Substudy C2: patients with SCLC, LCNEC and EP-NEC eligible for second line (2L) paclitaxel treatment.
    • Substudies C3 and C5: patients with SCLC eligible for 2L or 3L treatment with lurbinectedin (C3) or topotecan (C5) are eligible. Patients with SCLC who progressed on or were intolerant of DLL3-targeting therapies (including but not limited to tarlatamab) can be enrolled into substudies C3 or C5 for 3L treatment.
    • Substudy C4: patients with SCLC, LCNEC or EP-NEC eligible for 2L irinotecan, or patients with SCLC eligible for 3L irinotecan. Patients with SCLC who progressed on or were intolerant of DLL3-targeting therapies (including but not limited to tarlatamab) can be enrolled into substudy C4 for 3L treatment.

    Part D:

    • Substudy D1: will include 2L patients with SCLC, LCNEC, pr EP-NEC (excluding GEP-NEC) that have progressed/relapsed from their first-line treatment that may have included an ICI.
    • Substudy 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.
    • Substudy 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.
  4. 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.
  5. ECOG performance status of 0 or 1.
  6. 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.

Additional inclusion and exclusions criteria will 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 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.
Experimental: Part C: Chemotherapy Combination Therapy
Part C of the study will include substudies C1 to C5, 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.
Drug: Lurbinectedin
Administered per Standard of Care.
Drug: Irinotecan (drug)
Administered per Standard of Care.
Drug: Topotecan
Administered per Standard of Care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To determine recommended dose for expansion (RDE) of Peluntamig (PT217).
Time Frame: Through study completion, up to approximately 3 years.
Through study completion, up to approximately 3 years.
To evaluate the safety and tolerability of Peluntamig (PT217).
Time Frame: Through study completion, up to approximately 3 years.
Through study completion, up to approximately 3 years.
To evaluate the efficacy of Peluntamig (PT217) monotherapy or in combination treatments as assessed by ORR.
Time Frame: Through study completion, up to approximately 3 years.
Through study completion, up to approximately 3 years.

Secondary Outcome Measures

Outcome Measure
Time Frame
To evaluate the pharmacokinetics of Peluntamig (PT217).
Time Frame: Through study completion, up to approximately 3 years.
Through study completion, up to approximately 3 years.
To evaluate the immunogenicity (ADA) of Peluntamig (PT217).
Time Frame: Through study completion, up to approximately 3 years.
Through study completion, up to approximately 3 years.
To further evaluate the efficacy of Peluntamig (PT217) monotherapy or in combination treatments
Time Frame: Through study completion, up to approximately 3 years.
Through study completion, up to approximately 3 years.

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 (Actual)

July 15, 2026

Last Update Submitted That Met QC Criteria

July 13, 2026

Last Verified

July 1, 2026

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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