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

NCT05652686 | Recruiting Phase 1 FDA Drug

• 1 other identifier: PT217X1101
• Study Type: interventional
• Target: 203
• Locations: 1 country
• Sites: 15

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.

Conditions

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

Keywords

DLL3; DLL3 expressing tumors; Lung cancer; SCLC; LCNEC; NEPC; GEP-NEC; Small Cell Lung Cancer; Large cell neuroendocrine cancer; Neuroendocrine prostate cancer; Gastroenteropancreatic neuroendocrine carcinoma; Neuroendocrine carcinoma; Extrapulmonary neuroendocrine carcinoma; EP-NEC; CD47

Outcome Measures

Primary Outcomes (3)

• To determine recommended dose for expansion (RDE) of Peluntamig (PT217).

  Through study completion, up to approximately 3 years.

• To evaluate the safety and tolerability of Peluntamig (PT217).

  Through study completion, up to approximately 3 years.

• To evaluate the efficacy of Peluntamig (PT217) monotherapy or in combination treatments as assessed by ORR.

  Through study completion, up to approximately 3 years.

Secondary Outcomes (3)

• To evaluate the pharmacokinetics of Peluntamig (PT217).

  Through study completion, up to approximately 3 years.

• To evaluate the immunogenicity (ADA) of Peluntamig (PT217).

  Through study completion, up to approximately 3 years.

• To further evaluate the efficacy of Peluntamig (PT217) monotherapy or in combination treatments

  Through study completion, up to approximately 3 years.

Study Arms (4)

Part A: Dose Escalation

EXPERIMENTAL

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

Drug: Peluntamig (PT217)

Part B: Dose Expansion

EXPERIMENTAL

Part B cohorts will open after the dose level considered for RDE has been cleared in Parts A, C and D.

Drug: Peluntamig (PT217)

Part C: Chemotherapy Combination Therapy

EXPERIMENTAL

Part C of the study will include substudies C1 to C5, combining Peluntamig (PT217) with chemotherapy.

Drug: Peluntamig (PT217); Drug: Carboplatin + Etoposide; Drug: Paclitaxel.; Drug: Lurbinectedin; Drug: Irinotecan (drug); Drug: Topotecan

Part D: ICI Combination Therapy

EXPERIMENTAL

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

Drug: Peluntamig (PT217); Drug: Carboplatin + Etoposide; Drug: Atezolizumab

Interventions

Peluntamig (PT217) DRUG

A bispecific antibody (bsAb) against DLL3 and CD47.

Part A: Dose Escalation; Part B: Dose Expansion; Part C: Chemotherapy Combination Therapy; Part D: ICI Combination Therapy

Carboplatin + Etoposide DRUG

Administered per Standard of Care.

Part C: Chemotherapy Combination Therapy; Part D: ICI Combination Therapy

Lurbinectedin DRUG

Administered per Standard of Care.

Part C: Chemotherapy Combination Therapy

Irinotecan (drug) DRUG

Administered per Standard of Care.

Part C: Chemotherapy Combination Therapy

Topotecan DRUG

Administered per Standard of Care.

Part C: Chemotherapy Combination Therapy

Paclitaxel. DRUG

Administered per Standard of Care.

Part C: Chemotherapy Combination Therapy

Atezolizumab DRUG

Administered per Standard of Care.

Part D: ICI Combination Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

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.

Sponsors & Collaborators

• Phanes Therapeutics: lead
• Hoffmann-La Roche: collaborator

Study Sites (15)

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

Duarte, California, 91010, United States

RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

RECRUITING

Yale University Cancer Center

New Haven, Connecticut, 06520, United States

RECRUITING

Sidney Kimmel Comprehensive Cancer Center at John Hopkins

Baltimore, Maryland, 21287, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Washington University School of Medicine (Siteman Cancer Center)

St Louis, Missouri, 63108, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

Sarah Cannon Research Institute University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Providence Portland Medical Center

Portland, Oregon, 97213, United States

RECRUITING

Mays Cancer Center / University of Texas, San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Fred Hutch Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Carcinoma, Neuroendocrine; Lung Neoplasms

Interventions

EC regimen; Paclitaxel; atezolizumab; PM 01183; Irinotecan; Pharmaceutical Preparations; Topotecan

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Camptothecin; Alkaloids; Heterocyclic Compounds

Central Study Contacts

Phanes Therapeutics

CONTACT

858-766-0852; clinical-trials@phanestx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

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: July 15, 2026

Record last verified: 2026-07

Locations

US (15)