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

Zai Lab

Status and phase: Enrolling; Phase 1

Conditions: SCLC

Treatments: Drug: Carboplatin; Drug: ZL-1310; Drug: Atezolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06179069

ZL-1310-001

Details and patient eligibility

About

An open-label, multicenter study of ZL-1310 as a single agent and in combination with Atezolizumab (with and without Carboplatin) to evaluate the safety, efficacy, and pharmacokinetics in subjects with small cell lung cancer

Full description

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.

Enrollment: 112 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed informed consent
• Participant with metastatic or extensive-stage small cell lung cancer (de novo, not transformed) and for Part 1A and 1B must have documented disease progression during or following a platinum-based chemotherapy regimen. For Part 1C and Part 4, no prior systemic treatment for SCLC (including chemoradiotherapy for limited-stage SCLC). For Part 1B backfill, first-line setting: no prior systemic treatment for SCLC (including chemoradiotherapy for limited-stage SCLC); or, first-line maintenance setting: participants have received at least 4 cycles of 1L induction therapy with carboplatin or cisplatin, etoposide, and anti-PD-L1 inhibitor for ES-SCLC with ongoing CR, PR, or SD per RECIST v1.1 assessed by the investigator. For Part 3, participants have received at least 4 cycles of 1L induction therapy with carboplatin or cisplatin etoposide, and anti-PD-L1 inhibitor for ES-SCLC with ongoing CR, PR, or SD per RECIST v1.1 assessed by the investigator.
• 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

• Participants 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, Part 3, and Part 4 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 disease.

• 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.

• Inadequate organ function (as defined in protocol) within 10 days prior to the first dose of study treatment,

• Participants 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.

• Participants 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 but not limited to pneumonitis.

• Pregnant or nursing (lactating) women.

• Participants 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 and Part 4 (ZL-1310 in combination with Atezolizumab and Carboplatin), participants who received prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies.

• For Part 1B (ZL-1310 in combination with Atezolizumab) and Part 1C (ZL-1310 in combination with Atezolizumab and Carboplatin), participants who received systemic immunostimulatory agents (including but not limited to, IFNs and IL2) within 4 weeks or 5 drug-elimination half-lives, whichever is longer, prior to the initiation of study treatment.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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112 participants in 10 patient groups

Dose Escalation: Part 1A

Experimental group

Description:

ZL-1310 as a single-agent

Treatment:

Drug: ZL-1310

Dose Expansion: Part 1B

Experimental group

Description:

ZL-1310 in combination with Atezolizumab

Treatment:

Drug: Atezolizumab

Drug: ZL-1310

Dose Escalation: Part 1C

Experimental group

Description:

ZL-1310 in combination with Atezolizumab and Carboplatin as induction and followed by ZL-1310 and Atezolizumab as maintenance

Treatment:

Drug: Atezolizumab

Drug: ZL-1310

Drug: Carboplatin

Dose Expansion: Arm 1 (Part 2)

Experimental group

Description:

Dose level 1 of ZL-1310 established from single-agent dose-escalation

Treatment:

Drug: ZL-1310

Dose Expansion: Arm 2 (Part 2)

Experimental group

Description:

Dose level 2 of ZL-1310 established from single-agent dose escalation

Treatment:

Drug: ZL-1310

Dose Extension: Arm 1 (Part 2)

Experimental group

Description:

ZL-1310 as a single agent

Treatment:

Drug: ZL-1310

Doublet Dose Optimization: Arm 1 (Part 3)

Experimental group

Description:

Dose level 1 of ZL-1310 established from single agent dose escalation, in combination with Atezolizumab

Treatment:

Drug: Atezolizumab

Drug: ZL-1310

Doublet Dose Optimization: Arm 2 (Part 3)

Experimental group

Description:

Dose level 2 of ZL-1310 established from single agent dose escalation in combination with Atezolizumab

Treatment:

Drug: Atezolizumab

Drug: ZL-1310

Triplet Dose Optimization: Arm 1 (Part 4)

Experimental group

Description:

Dose level 1 of ZL-1310 established from single agent dose escalation in combination with Atezolizumab + Carboplatin induction followed by ZL-1310 + Atezolizumab as maintenance

Treatment:

Drug: Atezolizumab

Drug: ZL-1310

Drug: Carboplatin

Triplet Dose Optimization: Arm 2 (Part 4)

Experimental group

Description:

Dose level 2 of ZL-1310 established from single agent dose escalation, in combination with Atezolizumab + Carboplatin induction followed by ZL-1310 + atezolizumab as induction

Treatment:

Drug: Atezolizumab

Drug: ZL-1310

Drug: Carboplatin