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

NCT ID: NCT05652686

Last Updated: 2025-09-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

203 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-05

Study Completion Date

2028-08-31

Brief Summary

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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.

Detailed Description

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Conditions

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Small Cell Lung Cancer (SCLC) Large Cell Neuroendocrine Cancer (LCNEC) Neuroendocrine Prostate Cancer (NEPC) Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC) Neuroendocrine Carcinomas (NEC) Extrapulmonary Neuroendocrine Carcinoma (EP-NEC)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

The study will consist of 4 parts: Dose Escalation (Part A), Dose Expansion (Part B), Chemo Combination Therapy (Part C) and ICI combination Therapy (Part D).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part A: Dose Escalation

A standard 3+3 dose escalation design will be employed.

Group Type EXPERIMENTAL

Peluntamig (PT217)

Intervention Type DRUG

A bispecific antibody (bsAb) against DLL3 and CD47.

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.

Group Type EXPERIMENTAL

Peluntamig (PT217)

Intervention Type DRUG

A bispecific antibody (bsAb) against DLL3 and CD47.

Part C: Chemotherapy Combination Therapy

Part C of the study will include Cohorts C1 and C2, combining Peluntamig (PT217) with chemotherapy.

Group Type EXPERIMENTAL

Peluntamig (PT217)

Intervention Type DRUG

A bispecific antibody (bsAb) against DLL3 and CD47.

Carboplatin + Etoposide

Intervention Type DRUG

Administered per Standard of Care.

Paclitaxel.

Intervention Type DRUG

Administered per Standard of Care.

Part D: ICI Combination Therapy

In part D, Peluntamig (PT217) will be given in combination with atezolizumab, either alone or in combination with chemotherapy.

Group Type EXPERIMENTAL

Peluntamig (PT217)

Intervention Type DRUG

A bispecific antibody (bsAb) against DLL3 and CD47.

Carboplatin + Etoposide

Intervention Type DRUG

Administered per Standard of Care.

Atezolizumab

Intervention Type DRUG

Administered per Standard of Care.

Interventions

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Peluntamig (PT217)

A bispecific antibody (bsAb) against DLL3 and CD47.

Intervention Type DRUG

Carboplatin + Etoposide

Administered per Standard of Care.

Intervention Type DRUG

Paclitaxel.

Administered per Standard of Care.

Intervention Type DRUG

Atezolizumab

Administered per Standard of Care.

Intervention Type DRUG

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role collaborator

Phanes Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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City of Hope (City of Hope National Medical Center, City of Hope Medical Center)

Duarte, California, United States

Site Status RECRUITING

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States

Site Status RECRUITING

Sidney Kimmel Comprehensive Cancer Center at John Hopkins

Baltimore, Maryland, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Washington University School of Medicine (Siteman Cancer Center)

St Louis, Missouri, United States

Site Status RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

Sarah Cannon Research Institute University of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Providence Portland Medical Center

Portland, Oregon, United States

Site Status RECRUITING

The University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Site Status NOT_YET_RECRUITING

Mays Cancer Center / University of Texas, San Antonio

San Antonio, Texas, United States

Site Status RECRUITING

NEXT Virginia

Fairfax, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Phanes Therapeutics

Role: CONTACT

858-766-0852

Other Identifiers

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PT217X1101

Identifier Type: -

Identifier Source: org_study_id

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