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

Official title

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)

Overview

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.

Interventions

• Drug Peluntamig (PT217)
  A bispecific antibody (bsAb) against DLL3 and CD47.
• Drug Carboplatin + Etoposide
  Administered per Standard of Care.
• Drug Paclitaxel.
  Administered per Standard of Care.
• Drug Atezolizumab
  Administered per Standard of Care.
• Drug Lurbinectedin
  Administered per Standard of Care.
• Drug Irinotecan (drug)
  Administered per Standard of Care.
• Drug Topotecan
  Administered per Standard of Care.

Primary outcome measures

• To determine recommended dose for expansion (RDE) of Peluntamig (PT217). [Time frame: 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.]
• 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.]

Secondary outcome measures (3)

• To evaluate the pharmacokinetics of Peluntamig (PT217). [Time frame: 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.]
• To further evaluate the efficacy of Peluntamig (PT217) monotherapy or in combination treatments [Time frame: Through study completion, up to approximately 3 years.]

Eligibility criteria

Inclusion criteria

• 18 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.
• 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.

Exclusion criteria

• 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.

Additional inclusion and exclusions criteria will apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 15 centers

• City of Hope (City of Hope National Medical Center, City of Hope Medical Center) — Duarte
• USC Norris Comprehensive Cancer Center — Los Angeles
• Sarah Cannon Research Institute at HealthONE — Denver
• Yale University Cancer Center — New Haven
• Sidney Kimmel Comprehensive Cancer Center at John Hopkins — Baltimore
• Massachusetts General Hospital — Boston
• Dana-Farber Cancer Institute — Boston
• Washington University School of Medicine (Siteman Cancer Center) — St Louis
• … and 7 more centers

Identifiers

NCT: NCT05652686 · PT217X1101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗