Solid Tumors
Conditions
Brief summary
A Phase 1b/2, Open-label, Multi-center Study of ZL-1310 in Participants With Selected Solid Tumors
Detailed description
This is an open-label, multiple-center, phase 1b/2 study of ZL-1310 in selected solid tumors. ZL-1310 will be administered intravenously at 1.6 mg/kg every 21 days. Primary objectives include safety evaluation and confirmed objective response rate by blinded independent central review
Interventions
DRUGZL-1310
drug ZL-1310
Sponsors
Zai Lab (Shanghai) Co., Ltd.
Zai Lab (US) LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Adult men and women ≥18 years of age * Participants must have histologically confirmed, locally advanced or metastatic NeuroEndocrine Carcionomas (NEC) * Participants must be willing to undergo a tumor biopsy or must provide archived tumor tissue sample * Participants must have at least one measurable target lesion as defined by RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Life expectancy ≥ 3 months
Exclusion criteria
* Participants with another known malignancy that is progressing or requires active treatment within the last 2 years * Clinically active central nervous system (CNS) metastases * Participants with leptomeningeal metastasis * Participants who have received any ADC with a payload of topoisomerase I inhibitor (e.g., exatecan derivative)or had received topoisomerase I inhibitor (e.g., irinotecan) as the immediate prior therapy that the participant had progressed from. * Treatment with any systemic anti-cancer treatment or other investigational products/device within 3 weeks before the first dose of study treatment * Non-palliative radiotherapy within 2 weeks to non-thoracic area or within 4 weeks to the thoracic area prior to first dose of study treatment or 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 value (as defined in protocol) within 10 days prior to the first dose of study treatment * 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 * Has a history of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening * 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 dose of study treatment, whichever is longer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate antitumor activity of ZL-1310 as a single agent in Phase 2 | up to 36 months | Confirmed objective response rate (ORR) determined by blinded independent central review (BICR) in Phase 2 |
| Incidence of Treatment Emergent Adverse-Events in Phase 1b | up to 36 months | Number of subjects with treatment-emergent adverse events (TEAEs) |
| Incidence of Serious Adverse Events in Phase 1b | up to 36 months | Number of subjects with serious adverse events (SAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate durability of response in Phase 2 | up to 36 months | 1\. BICR- and investigator-determined duration of DOR in Phase 2 |
| Incidence of Treatment Emergent Adverse-Events in Phase 2 | up to 36 months | Number of subjects with treatment-emergent adverse events (TEAEs) |
| Incidence of Serious Adverse Events in Phase 2 | up to 36 months | Number of subjects with serious adverse events (SAEs) |
| Pharmacokinetics (PK): Time to maximum concentration (Tmax) of Total Antibody in all phases | up to 36 months | Time to maximum concentration (Tmax) is a pharmacokinetic parameter that refers to the time it takes for a drug or substance to reach its highest concentration in the bloodstream or a specific body compartment after administration |
| Pharmacokinetics (PK): maximum concentration (Cmax) of Total Antibody in all phases | up to 36 months | Maximum concentration (Cmax) is a key pharmacokinetic parameter. It represents the highest concentration of a drug or substance that is achieved in the bloodstream or a specific biological fluid or tissue after administration |
| Pharmacokinetics (PK): area under the concentration-time curve (AUC) of Total Antibody in all phases | up to 36 months | Area under the concentration-time curve (AUC) is a pharmacokinetic parameter that quantitatively describes the total exposure of a drug in the body over a specific period of time |
| Pharmacokinetics (PK): apparent clearance (CL) of Total Antibody in all phases | up to 36 months | Apparent clearance (CL) is a pharmacokinetic parameter that describes the rate at which a drug is removed from the body relative to the drug's concentration in the bloodstream or a specific body fluid |
| Pharmacokinetics (PK): terminal elimination half-life (T1/2) of Total Antibody in all phases | up to 36 months | Terminal elimination half-life (T1/2) is a pharmacokinetic parameter that characterizes the time it takes for the concentration of a drug in the body to decrease by half during the terminal phase of drug elimination |
| Evaluate preliminary antitumor activity of ZL-1310 as a single agent in Phase 1b | up to 36 months | 1. BICR-determined confirmed ORR in all cohorts 2. Investigator-determined confirmed ORR in all cohorts 3. BICR-determined 6-months progression-free survival (PFS6) rate in Cohort 3 4. Investigator-determined PFS6-rate in Cohort 3 |
| Pharmacokinetics (PK): maximum concentration (Cmax) of Unconjugated payloads in all phases | up to 36 months | Maximum concentration (Cmax) is a key pharmacokinetic parameter. It represents the highest concentration of a drug or substance that is achieved in the bloodstream or a specific biological fluid or tissue after administration |
| Pharmacokinetics (PK): area under the concentration-time curve (AUC) of Unconjugated payloads in all phases | up to 36 months | The area under the concentration - time curve (AUC) is a pharmacokinetic parameter that quantitatively describes the total exposure of a drug in the body over a specific period of time |
| Pharmacokinetics (PK): apparent clearance (CL) of Unconjugated payloads in all phases | up to 36 months | Apparent clearance (CL) is a pharmacokinetic parameter that describes the rate at which a drug is removed from the body relative to the drug's concentration in the bloodstream or a specific body fluid |
| Pharmacokinetics (PK): terminal elimination half-life (T1/2) of unconjugated payloads in all phases | up to 36 months | Terminal elimination half - life (T1/2) is a pharmacokinetic parameter that characterizes the time it takes for the concentration of a drug in the body to decrease by half during the terminal phase of drug elimination |
| Assess immunogenicity of ZL-1310 in all phases | up to 36 months | Incidence of anti-drug antibodies (ADAs) to ZL-1310 in all phases |
| Evaluate stability and control of disease in all phases | up to 36 months | BICR- and investigator-determined disease control rate (DCR) in all phases |
| Evaluate progression-free survival (PFS) in all phases | up to 36 months | BICR- and investigator-determined PFS in all phases |
| Evaluate survival in all phases | up to 36 months | Overall survival (OS) in all phases |
| Pharmacokinetics (PK): time to maximum concentration (Tmax) of Unconjugated payloads in all phases | up to 36 months | Time to maximum concentration (Tmax) is a pharmacokinetic parameter that refers to the time it takes for a drug or substance to reach its highest concentration in the bloodstream or a specific body compartment after administration |
| Evaluate durability of response in Phase 1b | up to 36 months | 1\. BICR- and investigator-determined duration of response (DOR) in Phase 1b |
| Evaluate preliminary antitumor activity of ZL-1310 as a single agent in Phase 2 | up to 36 months | Investigator-determined confirmed ORR in Phase 2 |
Countries
China, United States
Contacts
CONTACTZaiLab_1310-002_StudyTeam
Outcome results
None listed