Extrapulmonary Neuroendocrine Carcinoma (EP-NEC), Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC), Large Cell Neuroendocrine Cancer (LCNEC), Neuroendocrine Carcinomas (NEC), Neuroendocrine Prostate Cancer (NEPC), Small Cell Lung Cancer (SCLC)
Conditions
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
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.
Interventions
DRUGPeluntamig (PT217)
A bispecific antibody (bsAb) against DLL3 and CD47.
Administered per Standard of Care.
DRUGPaclitaxel.
Administered per Standard of Care.
DRUGAtezolizumab
Administered per Standard of Care.
DRUGLurbinectedin
Administered per Standard of Care.
Administered per Standard of Care.
DRUGTopotecan
Administered per Standard of Care.
Sponsors
Phanes Therapeutics
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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. |
Countries
United States
Contacts
CONTACTPhanes Therapeutics
Outcome results
None listed