A Study of ZL-1310 in Subjects With Small Cell Lung Cancer

An Open-label, Multicenter Study of ZL-1310 as a Single Agent and In Combination with Atezolizumab to Evaluate the Safety, Tolerability, and Pharmacokinetics in Subjects with Small Cell Lung Cancer

This is an open-label, ascending, multiple-dose, phase 1 study evaluating ZL-1310 as a single agent, in combination with Atezolizumab, and in combination with Atezolizumab and Carboplatin in subjects with extensive SCLC.

Eligibility Criteria:
Inclusion Criteria:

* Signed informed consent
* Subjects must have histologically or cytologically confirmed metastatic or extensive-stage small cell lung cancer with documented disease progression during or following a platinum-based chemotherapy regimen. No more than 3 prior regimens in the metastatic or extensive stage are allowed.
* Adult men and women ≥18 years of age. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Subjects must have at least one measurable target lesion as defined by RECIST v1.1 on CT, PET/CT, or MRI.
* Subjects must be willing to undergo a tumor biopsy or must provide archived tumor tissue sample at screening per protocol guidelines.
* Life Expectancy \>3 months.

Exclusion Criteria:

* Subjects with another known malignancy that is progressing or requires active treatment within the last 2 years. Exceptions: basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin with previously administered curative treatment, in situ cervical cancer, or other cancers that do not require systemic anti-cancer therapies and will not impact life expectancy.
* Symptomatic or untreated brain metastasis requiring concurrent treatment. For Part 2, the following subjects can be enrolled if they have a stable neurologic status for at least 2 weeks prior to the first dose of ZL-1310:

  1. Subjects with untreated and asymptomatic brain metastases.
  2. Subjects with treated brain metastases that are no longer symptomatic (i.e. without neurologic signs or symptoms), who require no treatment with steriods or anticonvulsants and have recovered from the actue toxic effects of radiotherapy.
* Subjects with leptomeningeal metastasis.
* Treatment with any systemic anti-cancer treatment or other investigational products/ device within 3 weeks before first dose of study treatment.
* Non-palliative radiotherapy within 2 weeks prior to first dose of study treatment or have had a history of radiation pneumonitis.
* Major surgery within 4 weeks of the first dose of study treatment.
* Hypersensitivity to any ingredient of the study treatment.
* Out of range lab value (as defined in protocol) within 10 days prior to the first dose of study treatment,
* Subjects with a diagnosis of immunodeficiency or receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 14 days or 5 half-lives before the first dose of study treatment, whichever is longer.
* Subjects have received a live or live-attenuated vaccine within 30 days of planned start of study therapy.
* Impaired cardiac function or clinically significant cardiac disease within the last 3 months before administration of the first dose of the study treatment
* Lung-specific intercurrent clinically significant illnesses and any autoimmune, connective tissue, or inflammatory disorders, including not limited to pneumonitis.
* Pregnant or nursing (lactating) women.
* Subjects who have been on concomitant strong CYP3A or CYP2D6 inhibitors within 14 days or 5 half-lives before the first study treatment, whichever is longer.
* For Part 1C only (ZL-1310 in combination with Atezolizumab and Carboplatin), subjects who received prior treatment with CD137agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
* For Part 1B (Z-1310 in combination with Atezolizumab) and Part 1C (ZL-1310 in combination with Atezolizumab and Carboplatin), subjects who received systemic immunostimulatory agents (including but not limited to, IFNs and IL2) within 4 weeks or 5 drug-elimination half-lives prior to the initiation of study treatment.