A Study of Peluntamig (PT217) in Patients With Neuroendocrine Carcinomas Expressing DLL3 (the SKYBRIDGE Study)
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)
1 other identifier
interventional
203
1 country
12
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2023
Longer than P75 for phase_1
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 7, 2022
CompletedFirst Posted
Study publicly available on registry
December 15, 2022
CompletedStudy Start
First participant enrolled
September 5, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 1, 2028
September 23, 2025
September 1, 2025
4.2 years
December 7, 2022
September 18, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
To determine the dose-limiting toxicity (DLT) of Peluntamig (PT217).
Through study completion.
To determine the maximum tolerated dose (MTD) of Peluntamig (PT217) if reached.
Through study completion.
To determine recommended dose for expansion (RDE) of Peluntamig (PT217).
Through study completion.
To evaluate the safety and tolerability of Peluntamig (PT217).
Through study completion.
To evaluate the efficacy of Peluntamig (PT217) monotherapy or in combination treatments
Through study completion
Secondary Outcomes (3)
To evaluate the pharmacokinetics of Peluntamig (PT217).
Through study completion.
To evaluate the immunogenicity (ADA) of Peluntamig (PT217).
Through study completion.
To further evaluate the efficacy of Peluntamig (PT217) monotherapy or in combination treatments
Through study completion.
Study Arms (4)
Part A: Dose Escalation
EXPERIMENTALA standard 3+3 dose escalation design will be employed.
Part B: Dose Expansion
EXPERIMENTALPart B cohorts will open after the dose level considered for RDE has been cleared in Parts A, C and D.
Part C: Chemotherapy Combination Therapy
EXPERIMENTALPart C of the study will include Cohorts C1 and C2, combining Peluntamig (PT217) with chemotherapy.
Part D: ICI Combination Therapy
EXPERIMENTALIn part D, Peluntamig (PT217) will be given in combination with atezolizumab, either alone or in combination with chemotherapy.
Interventions
A bispecific antibody (bsAb) against DLL3 and CD47.
Administered per Standard of Care.
Eligibility Criteria
You may qualify if:
- 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.
- 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.
- ECOG performance status of 0 or 1.
- Adequate organ function confirmed at screening and within 72 hours of initiating C1D1 of Peluntamig (PT217) treatment.
You may not qualify if:
- Women who are pregnant or lactating.
- Women of child-bearing potential (WOCBP) who do not use adequate birth control.
- Autoimmune disease requiring systemic treatment within the past twelve months.
- 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).
- 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).
- Patients who have experienced Grade ≥ 3 immune-related events, such as (non-infectious) pneumonitis, interstitial lung disease, myocarditis.
- Treatment with therapeutic oral or i.v. antibiotics within 2 weeks prior to initiation of study treatment with Peluntamig (PT217).
- 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.
- Impaired cardiac function or significant diseases.
- For Part D only, uncontrolled hypercalcemia.
- 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.
- Prior hemolytic anemia or Evans Syndrome in the last 3 months.
- Patients who have Grade ≥ 3 neuropathy.
- Patients who are currently receiving treatment with therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants .
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Phanes Therapeuticslead
- Hoffmann-La Rochecollaborator
Study Sites (12)
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte, California, 91010, United States
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, 80218, United States
Sidney Kimmel Comprehensive Cancer Center at John Hopkins
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Washington University School of Medicine (Siteman Cancer Center)
St Louis, Missouri, 63108, United States
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599, United States
Sarah Cannon Research Institute University of Oklahoma
Oklahoma City, Oklahoma, 73104, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
The University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030, United States
Mays Cancer Center / University of Texas, San Antonio
San Antonio, Texas, 78229, United States
NEXT Virginia
Fairfax, Virginia, 22031, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 7, 2022
First Posted
December 15, 2022
Study Start
September 5, 2023
Primary Completion (Estimated)
December 1, 2027
Study Completion (Estimated)
August 1, 2028
Last Updated
September 23, 2025
Record last verified: 2025-09