A Phase 1 Study of SAIL66 in Patients With CLDN6-positive Locally Advanced or Metastatic Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This is a Phase 1 dose-escalation and expansion study that will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of SAIL66 in patients with CLDN6-positive locally advanced or metastatic solid tumors.

Official Title
-----------------
A Phase I Open-label, Multicenter Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of SAIL66 in Patients With CLDN6-positive Locally Advanced or Metastatic Solid Tumors

Conditions
-----------------
Solid Tumor

Intervention / Treatment
-----------------
* Drug: SAIL66
* Drug: Tocilizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years at time of signing Informed Consent Form Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 Patients with CLDN6 positive solid tumors Exclusion Criteria: Intending to become pregnant or breastfeed during the study and within 3 months after the last dose of SAIL66 or tocilizumab, whichever is longer Primary central nervous system (CNS) malignancy, symptomatic (seizures etc.) CNS metastases, actively progressing CNS metastases or CNS metastases required any anti-cancer treatment History or presence of CNS disease such as stroke (e.g., subarachnoid hemorrhage or cerebral infarction), epilepsy, CNS vasculitis, neurodegenerative disease, aphasia, dementia or paresis Uncontrolled tumor-related pain Uncontrolled pleural effusion, pericardial effusion, or ascites

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part1: Dose Escalation part<br>Patients will receive SAIL66 as a IV infusion at escalated doses. | Drug: SAIL66<br>* SAIL66 as a IV infusion<br>Drug: Tocilizumab<br>* Tocilizumab as a IV infusion<br>|
| Experimental: Part2: Expansion part<br>Patients will receive SAIL66 as a IV infusion at the recommended dose. | Drug: SAIL66<br>* SAIL66 as a IV infusion<br>Drug: Tocilizumab<br>* Tocilizumab as a IV infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events of SAIL66[safety and tolerability] | Incidence, nature, and severity of adverse events graded according to NCI Common Terminology CTCAE v5.0, with severity of CRS determined according to the American Society for Transplantation and Cell Therapy (ASTCT) Consensus Grading Criteria | From screening until study completion, treatment discontinuation or post-treatment follow up (approximately 18 weeks) | 
| Change from baseline in vital signs[safety and tolerability] | Change from baseline in vital signs | From screening until study completion or treatment discontinuation (approximately 18 weeks) | 
| Change from baseline in clinical laboratory test results and examination findings[safety and tolerability] | Change from baseline in clinical laboratory test results and examination findings specified in this study including, but not limited, electrocardiograms (ECGs) | From screening until study completion or treatment discontinuation (approximately 18 weeks) | 
| Dose-limiting toxicities (DLTs) of SAIL66[safety and tolerability] | Incidence and nature of the DLTs | From Cycle 1 Day 1 until Cycle 1 Day 21 (Cycle 1 is 21 days) | 
| Preliminary anti-tumor activity of SAIL66 when administered at selected dose(s) in each cohort [Part 2] | Objective response rate (ORR), defined as the proportion of patients with a confirmed complete response (CR) or partial response (PR) on two consecutive occasions >= 4 weeks apart, assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 by the investigators. | From screening until study completion, treatment discontinuation or post-treatment follow up (approximately 18 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum serum concentration (Cmax) of SAIL66[PK profile] | Maximum serum concentration (Cmax) of SAIL66 | From screening until study completion, treatment discontinuation or post-treatment follow up (approximately 18 weeks) | 
| Trough serum concentration (Ctrough) of SAIL66[PK profile] | Trough serum concentration (Ctrough) of SAIL66 | From screening until study completion, treatment discontinuation or post-treatment follow up (approximately 18 weeks) | 
| Area under the concentration time-curve (AUC) of SAIL66[PK profile] | Area under the concentration time-curve (AUC) of SAIL66 | From the first occurrence of CR or PR to progression disease (PD) or death from any cause (whichever occurs first) (approximately 18 weeks) | 
| Objective response rate(ORR)[preliminary efficacy] | ORR assessed per RECIST v.1.1 by the investigators. [Part 1] | From screening until study completion, treatment discontinuation or post-treatment follow up (approximately 18 weeks) | 
| Duration of response (DoR)[preliminary efficacy] | Duration of response (DoR), defined as the time from the first occurrence of CR or PR to progression disease (PD) or death from any cause (whichever occurs first), per the investigator according to RECIST v.1.1 | From the first occurrence of CR or PR to progression disease (PD) or death from any cause (whichever occurs first)(whichever occurs first) (approximately 18 weeks) | 
| Disease control rate (DCR)[preliminary efficacy] | Disease control rate (DCR), defined as the proportion of patients who have CR, PR, or stable disease (SD) as best overall response per RECIST v.1.1 as determined by the investigator. SD must be confirmed at the first tumor assessment as scheduled in Appendix 1 after the start of treatment (the minimum duration for SD). | From screening until study completion, treatment discontinuation or post-treatment follow up (approximately 18 weeks) | 
| Progression-free survival (PFS)[preliminary efficacy] | Progression-free survival (PFS), defined as the time from administration of first study treatment to the first occurrence of disease progression or death from any cause, as determined by the investigator according to RECIST v.1.1 | From administration of first study treatment to the first occurrence of disease progression or death from any cause (approximately 18 weeks) | 
| Overall survival (OS)[preliminary efficacy] | Overall survival (OS), defined as the time from administration of first study treatment to death from any cause [Part 2] | From administration of first study treatment to death from any cause (approximately 18 weeks) | 
| Immunogenicity of SAIL66[preliminary efficacy] | Incidence of ADAs to SAIL66 and potential correlation with PK parameters and safety | From Cycle 1 Day 1 (Cycle 1 is 21 days) until study completion or treatment discontinuation (approximately 18 weeks) |