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Dose escalation: GI-102, multiple ascending doses

Dose escalation phase:

GI-102 will be administered via IV infusion Q3W up to 2 years (approximately 35 cycles).

GI-102

Dose expansion phase:

GI-102 will be administered via IV infusion Q3W up to 2 years (approximately 35 cycles).

Jay Kim

Woosun Lee

Mahesh Seetharam

Yujie Zhao

Jian Li Campian, PhD.

Wen Wee Ma, M.B.B.S

Seock-Ah Im, M.D., Ph.D.

Byoung Chul Cho, M.D., Ph.D.

Jung-Yun Lee, M.D., Ph.D.

Jae Lyun Lee, M.D., Ph.D.

Jeeyun Lee, M.D., Ph.D.

Byoung Yong Shim, M.D., Ph.D.

Nari Yun, PhD

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-102 as a single agent over a range of advanced and/or metastatic solid tumors.

This is a phase 1/2a, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, and anti-tumor effect of GI-102 as a single agent over a range of advanced and/or metastatic solid tumors. This study is adaptive in nature. While GI-102 is being investigated as a single agent in this trial, GI-102 has the potential of being combined with other agents. Based on the data from ongoing nonclinical studies and the dose escalation phase, additional combination therapies \[GI-102 + drug(s) X\] may be proposed and added to this study protocol via an amendment.

This study will comprise two phases.

* GI-102 monotherapy dose escalation phase
* GI-102 monotherapy dose expansion phase

GI-102 is a novel bi-specific Fc fusion protein containing the CD80 ectodomain as an N-terminal moiety and an interleukin (IL)-2 variant as a C-terminal moiety configurated via a human immunoglobulin G4 (IgG4) Fc. GI-102 has unique characteristics by having bispecificity to CD80 and IL2Rβγ. The CD80 portion is responsible for targeting tumor/immune cells while blocking CTLA-4 expressed on the Treg cells. The IL-2v of GI-102 is designed to abolish IL-2Rα affinity and therefore minimize the effect on Treg while it has very outstanding effect on NK and CD8 T cell proliferation and activity through IL-2Rbr affinity.

A Study to Evaluate the Safety and Therapeutic Activity of GI-102 in Patients With Advanced Solid Tumors

An Open-label, Multicenter, Dose Escalation and Expansion Phase 1/2a Study to Evaluate the Safety, Tolerability and Pharmacokinetics, and Therapeutic Activity of GI-102 in Patients With Advanced or Metastatic Solid Tumors

Serum will be assessed for the presence of ADA and Nab based on the appropriate assay.

CD4+ T cells in peripheral blood will be assessed by flow cytometry at various time points

CD8+ T cells in peripheral blood will be assessed by flow cytometry at various time points

Treg cells in peripheral blood will be assessed by flow cytometry at various time points

A DLT is defined as a clinically significant AE (classified according to the NCI CTCAE version 5) or significant laboratory abnormality that occur during the DLT assessment periods, during dose escalation and dose expansion, and is considered by the Investigator to be related to GI-102.

An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. All AE events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

ORR is defined as the percentage of participants with investigator-assessed objective response of complete response (CR) or partial response (PR). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).

DCR is defined as the percentage of patients who have achieved CR, PR and stable disease (SD), per RECIST v1.1 guideline as determined by the investigators.

DCR is defined as the time from the first occurrence of a documented objective response to the time of the first document disease progression or death from any cause, whichever occurs first, per RECIST v1.1 as determined by the investigator.

PFS is defined as the time from the first study treatment (Day 1) to the first occurrence of progression or death from any cause, whichever occurs first, per RECIST v1.1 guideline as determined by the investigator

OS is defined as the time from the first study treatment to death from any cause

Based on the concentration vs time profile by dose level

Spots Global Cancer Trial Database for bispecific protein