IBI334 in Subjects With Unresectable, Locally Advanced or Metastatic Solid Tumors

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study to evaluate the safety and tolerability of IBI334 and determine the maximum tolerated dose (MTD) and the recommended Phase 2 Dose (RP2D) of IBI334.

Official Title
-----------------
A Phase I/II Study of IBI334 in Subjects With Unresectable, Locally Advanced or Metastatic Solid Tumors

Conditions
-----------------
Solid Tumors

Intervention / Treatment
-----------------
* Drug: IBI334 D
* Drug: IBI334 C
* Drug: IBI334 A
* Drug: IBI334 B
* Drug: IBI334 F
* Drug: IBI334 E


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria： Male or female subjects ≥ 18 years old; Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1; Anticipated life expectancy of ≥ 12 weeks; Adequate bone marrow and organ function; Criteria for dose escalation phase only: Has a documented (histologically- or cytologically-proven), unresectable, locally advanced or metastatic solid tumor that is refractory to or intolerable with standard treatment, or for which no standard treatment is available (mainly focused on non-small-cell lung cancer, head and neck squamous cell carcinoma and RAS-wildtype colorectal cancer); At least 1 evaluable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; Criteria for dose expansion phase only: Has a documented (histologically- or cytologically-proven), unresectable, locally advanced or metastatic non-small-cell lung cancer, head and neck squamous cell carcinoma or RAS-wildtype colorectal cancer that is refractory to or intolerable with standard treatment, or for which no standard treatment is available; At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Exclusion Criteria： Participate in any other interventional clinical research except observational (non-interventional) study or in the follow-up phase of the interventional study; Received live vaccines within 4 weeks prior to first dose of the study drug or plan on receiving any live vaccine during the study; Received total pelvic radiotherapy; Pyloric obstruction and/or persistent recurrent vomiting (≥ 3 times in 24 hours); Uncontrolled diseases; History of endotracheal or gastrointestinal stent implantation; Multiple concurrent malignant tumors within 5 years (except non-melanoma skin cancer, carcinoma in situ or non-invasive tumor that were cured); Women who are pregnant, have positive results in pregnancy test or are lactating; Not eligible to participate in this study at the discretion of the investigator.

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: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI334 E<br> | Drug: IBI334 E<br>* Subjects will receive IBI334 C once a week during the first 28-day cycle (QW, 4 weeks), then biweekly (or other dose intervals recommended by the Investigator and Sponsor based on safety, toxicity and PK data), until disease progression, toxicity intolerance, withdrawal of consent, occurrence of other reasons for discontinuing study therapy, or treatment duration reaches 24 months, whichever occurs first.<br>|
| Experimental: IBI334 D<br> | Drug: IBI334 D<br>* Subjects will receive IBI334 D once a week during the first 28-day cycle (QW, 4 weeks), then biweekly (or other dose intervals recommended by the Investigator and Sponsor based on safety, toxicity and PK data), until disease progression, toxicity intolerance, withdrawal of consent, occurrence of other reasons for discontinuing study therapy, or treatment duration reaches 24 months, whichever occurs first.<br>|
| Experimental: IBI334 C<br> | Drug: IBI334 C<br>* Subjects will receive IBI334 C once a week during the first 28-day cycle (QW, 4 weeks), then biweekly (or other dose intervals recommended by the Investigator and Sponsor based on safety, toxicity and PK data), until disease progression, toxicity intolerance, withdrawal of consent, occurrence of other reasons for discontinuing study therapy, or treatment duration reaches 24 months, whichever occurs first.<br>|
| Experimental: IBI334 A<br> | Drug: IBI334 A<br>* Subjects will receive IBI334 A once a week during the first 28-day cycle (QW, 4 weeks), then biweekly (or other dose intervals recommended by the Investigator and Sponsor based on safety, toxicity and PK data), until disease progression, toxicity intolerance, withdrawal of consent, occurrence of other reasons for discontinuing study therapy, or treatment duration reaches 24 months, whichever occurs first.<br>|
| Experimental: IBI334 F<br> | Drug: IBI334 F<br>* Subjects will receive IBI334 F once a week during the first 28-day cycle (QW, 4 weeks), then biweekly (or other dose intervals recommended by the Investigator and Sponsor based on safety, toxicity and PK data), until disease progression, toxicity intolerance, withdrawal of consent, occurrence of other reasons for discontinuing study therapy, or treatment duration reaches 24 months, whichever occurs first.<br>|
| Experimental: IBI334 B<br> | Drug: IBI334 B<br>* Subjects will receive IBI334 B once a week during the first 28-day cycle (QW, 4 weeks), then biweekly (or other dose intervals recommended by the Investigator and Sponsor based on safety, toxicity and PK data), until disease progression, toxicity intolerance, withdrawal of consent, occurrence of other reasons for discontinuing study therapy, or treatment duration reaches 24 months, whichever occurs first.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with treatment-related adverse events | Number of patients who experienced a treatment related AEs from the first dose until 60 days after the last dose | Up to 60 days post last dose | 
| Percentage of subjects woth Dose-Limitine toxicities(DLTs) | To evaluate the safety and tolerability of IBI334 | Up to 28 days following first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Objective Response Rate (ORR) is the percentage of Complete Response (CR) plus partial response(PR) assessed per RECIST v1.1 criteria . | Up to 60 days post last dose | 
| Duration of response (DoR) | For subjects with CR or PR, duration of response(DoR) is the time from the first documented CR or PR to disease progression or death assessed per RECIST V1.1 criteria. | Up to 60 days post last dose | 
| Disease control rate (DCR) | Disease control rate (DCR) is the percentage of CR plus PR Plus stable disease (SD) assessed per RECIST v1.1 criteria. | Up to 60 days post last dose | 
| Time to Response (TTR) | For subjects with CR or PR, time to response(TTR) is the time from first dose of study drugs to the first documented CR or PR assessed per RECIST v1.1 criteria. | Up to 60 days post last dose | 
| Progression-free survival (PFS) | Time from randomization to first documented disease progression (radiographic) assessed by investigator per RECIST v1.1 criteria or death due to any cause. | Up to 60 days post last dose | 
| Overall survival (OS) | Time from randomization to death of the subject due to any cause. | Up to 60 days post last dose |