JAB-3068 Activity in Adult Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of JAB-3068 administered in investigational regimens in adult participants with advanced solid tumors.

Detailed Description
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To assess the safety and tolerability and determine the recommended phase 2 dose (RP2D) of JAB-3068 in combination with PD1 inhibitor in patients with advanced solid tumors.

Official Title
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A Phase 1b/2a, Multi-Center, Open-Label，Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of JAB-3068 in Combination With JS001 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor, Esophageal Squamous Cell Carcinoma, Non Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: JAB-3068
* Drug: PD1 inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent, according to local guidelines, signed and dated by the participant prior to the performance of any study-specific procedures, sampling, or analyses. Participant must be ≥18 years of age at the time of signature of the informed consent form (ICF). Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Exclusion Criteria: History (≤3 years) of cancer that is histologically distinct from the cancers under study, except for cervical carcinoma in situ, superficial non-invasive bladder tumors, or curatively treated Stage I non-melanoma skin cancer Known serious allergy to experimental drugs Brain or spinal metastases, except if treated by surgery, surgery plus radiotherapy or radiotherapy alone, with no evidence of progression or hemorrhage for ≤21 days before the start of treatment with the study drugs, and has not received any systemic corticosteroids for ≥21 days before the start of treatment with the study drugs

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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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: JAB-3068+PD1 inhibitor Part1<br>JAB-3068+JS001 dose escalation | Drug: JAB-3068<br>* JAB-3068 administrated orally as a tablet.<br>Drug: PD1 inhibitor<br>* JS001 administrated as an intravenous(IV) infusion.<br>|
| Experimental: JAB-3068+PD1 inhibitor Part2<br>JAB-3068+JS001 dose expansion | Drug: JAB-3068<br>* JAB-3068 administrated orally as a tablet.<br>Drug: PD1 inhibitor<br>* JS001 administrated as an intravenous(IV) infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with dose limiting toxicities | Incidence of dose limiting toxicities (DLTs) . A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first treatment cycle with JAB-3068 and JS001. | 24 months | 
| Objective response rate (ORR) | ORR is defined as the proportion of participants with complete response or partial response (CR+PR). | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration (Cmax) | Highest observed plasma concentration of JAB-3068 and JS001 | 24 months | 
| Time to achieve Cmax (Tmax) | Time of highest observed plasma concentration of JAB-3068 and JS001 | 24 months | 
| Area under the plasma concentration-time curve (AUC) | Area under the plasma concentration time curve of JAB-3068 and JS001 | 24 months | 
| Duration of response ( DCR ) | DCR is defined as proportion of participants with complete response, partial response, stable disease(CR+PR+SD). | 24 months | 
| Progression-free survival (PFS) | PFS is defined as the interval of time between the date of first treatment to the earliest date of disease progression or death which occurs first. | 24 months | 
| Duration of response ( DOR ) | DOR is defined as the time from the participant's initial objective response (CR or PR) to study drug therapy, to disease progression or death due to any cause, whichever occurs first. | 24 months | 
| Overall survival (OS) | OS is defined as the interval of time between the date of first treatment until death, loss to follow up or termination of the study by the sponsor. | 24 months | 
| Number of Participants with Treatment-related Adverse Events(TRAE) | TRAE is defined as the AES that the casual relationship of the AE is ralated to investigational drug. | 24 months |