Clinical trial NCT06179069: A Study of ZL-1310 in Subjects With Small Cell Lung Cancer
Official title: An Open-label, Multicenter Study of ZL-1310 to Evaluate the Safety, Efficacy, and Pharmacokinetics in Participants With Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: SCLC
Lead sponsor: Zai Lab (Hong Kong), Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Zai Lab (US) LLC
First posted: 2023-12-21
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities of ZL-1310 as a single agent (Part 1A), in combination with Atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 1C)
timeFrame: up to 24 months
measure: Incidence of Treatment Emergent Adverse-Events of ZL-1310 as a single agent (Part 1A), in combination with atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 1C)
timeFrame: up to 24 months
measure: Incidence of Serious Adverse Events of ZL-1310 as a single agent (Part 1A), in combination with atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 1C)
timeFrame: up to 24 months
measure: Incidence of Treatment Emergent Adverse Events of ZL-1310 as a single agent (Part 2), in combination with atezolizumab (Part 3) and in combination with atezolizumab and carboplatin (Part 4)
timeFrame: up to 24 months
measure: Incidence of Serious Adverse-Events (SAEs) of ZL-1310 as a single agent (Part 2), in combination with atezolizumab (Part 3), and in combination with atezolizumab and carboplatin (Part 4)
timeFrame: up to 24 months
measure: Antitumor activity per RECIST v1.1 by investigator's assessment of ZL-1310 as a single agent (Part 2), in combination with atezolizumab (Part 3), and in combination with atezolizumab and carboplatin (Part 4)
timeFrame: up to 24 months
measure: Objective response rate (ORR) per RECIST v1.1 of ZL-1310 as a single agent (Part 2) and in combination with atezolizumab and carboplatin (Part 4)
timeFrame: up to 24 months
measure: Disease control rate (DCR) per RECIST v1.1 of ZL-1310 in combination with atezolizumab
timeFrame: up to 24 months
Secondary outcomes:
measure: Objective response rate (ORR) per RECIST 1.1 of ZL-1310 as a single agent (Part 1A) in combination with atezolizumab (Part 1B), in combination with atezolizumab and carboplatin (Part 1C, Part 3)
timeFrame: up to 24 months
measure: Disease control rate (DCR) per RECIST v1.1 of ZL-1310 as a single agent (Part 1A and Part 2), in combination with atezolizumab (Part 1B), and in combination with atezolizumab and carboplatin (Part 4)
timeFrame: up to 24 months
measure: Duration of response per RECIST v1.1
timeFrame: up to 24 months
measure: Progression free survival per RECIST v1.1
timeFrame: up to 24 months
measure: Overall Survival of ZL-1310
timeFrame: up to 24 months
measure: Pharmacokinetics: Total Antibody of ZL-1310
timeFrame: up to 24 months
measure: Pharmacokinetics: Unconjugated payloads of ZL-1310
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: Zai Lab Site 2005
state: California
city: New Haven
country: United States
facility: Zai Lab Site 2030
state: Connecticut
city: Sarasota
country: United States
facility: Zai Lab Site 2026
state: Florida
city: Detroit
country: United States
facility: Zai Lab Site 2013
state: Michigan
city: Hackensack
country: United States
facility: Zai Lab Site 2001
state: New Jersey
city: Buffalo
country: United States
facility: Zai Lab Site 2002
state: New York
city: Durham
country: United States
facility: Zai Lab Site 2018
state: North Carolina
city: Cleveland
country: United States
facility: Zai Lab Site 2024
state: Ohio
city: Pittsburgh
country: United States
facility: Zai Lab Site 2029
state: Pennsylvania
city: Charleston
country: United States
facility: Zai Lab Site 2012
state: South Carolina
city: Fairfax
country: United States
facility: Zai Lab Site 2006
state: Virginia
city: Hefei
country: China
facility: Zai Lab Site 1004
state: Anhui
city: Beijing
country: China
facility: Zai Lab Site 1005
state: Beijing
city: Xiamen
country: China
facility: Zai Lab Site 1012
state: Fujian
city: Guangzhou
country: China
facility: Zai Lab Site 1001
state: Guangdong
city: Harbin
country: China
facility: Zai Lab Site 1009
state: Heilongjiang
city: Zhengzhou
country: China
facility: Zai Lab Site 1006
state: Henan
city: Wuhan
country: China
facility: Zai Lab 1002
state: Hubei
city: Changsha
country: China
facility: Zai Lab Site 1014
state: Hunan
city: Nanjing
country: China
facility: Zai Lab Site 1016
state: Jiangsu
city: Nanchang
country: China
facility: Zai Lab Site 1003
state: Jiangxi
city: Ch'ang-ch'un
country: China
facility: Zai Lab Site 1008
state: Jilin
city: Shenyang
country: China
facility: Zai Lab Site 1017
state: Liaoning
city: Xi'an
country: China
facility: Zai Lab Site 1015
state: Shaanxi
city: Jinan
country: China
facility: Zai Lab Site 1011
state: Shandong
city: Shanghai
country: China
facility: Zai Lab Site 1010
state: Shanghai
city: Chengdu
country: China
facility: Zai Lab Site 1013
state: Sichaun
city: Barcelona
country: Spain
facility: Zai Lab Site 8007
city: Barcelona
country: Spain
facility: Zai Lab Site 8002
city: Madrid
country: Spain
facility: Zai Lab Site 8003
city: Madrid
country: Spain
facility: Zai Lab Site 8006
city: Madrid
country: Spain
facility: Zai Lab Site 8009
city: Málaga
country: Spain
facility: Zai Lab Site 8008
city: Pozuelo De Alarcón
country: Spain
facility: Zai Lab Site 8010
city: Sevilla
country: Spain
facility: Zai Lab Site 8005
city: Sevilla
country: Spain
facility: Zai Lab Site 8011
city: Valencia
country: Spain
facility: Zai Lab Site 8004
city: Valencia
country: Spain
facility: Zai Lab Site 8001
Study officials:
References: