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

Eligibility Criteria

Key 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 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 and EP-NEC eligible for first-line (1L) CE treatment, or 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 second line (2L) CE treatment.

Cohort C2: patients with SCLC, LCNEC and EP-NEC eligible for second line (2L) paclitaxel treatment.

Part D:
* Cohort D1: will include second-line (2L) patients with LCNEC, EP-NEC or ES-SCLC that have progressed/relapsed from their first-line treatment that may have included an ICI.
* Cohort D2: will include first-line (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 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. Biopsy must be excisional, incisional, or core needle. This biopsy may not be done if the biopsy poses a risk to the patient and/or per the Investigator's discretion.
3. ECOG performance status of 0 or 1.
4. Adequate organ function confirmed at screening and within 72 hours of initiating C1D1 of 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.
4. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment with 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 PT217, or anticipation of need for systemic immunosuppressive medication during study drug 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 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 enrollment.
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.