CTRI/2025/02/080062 [Registered on: 07/02/2025] Trial Registered Prospectively
Last Modified On:
06/01/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
First-in-human (FIH), dose escalation study with enrichments and dose expansion, designed to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary antitumor activity of GIM-122 in adults with advanced solid malignancies.
Scientific Title of Study
A First-in-Human, Open-Label, Phase 1/2 Dose-Escalation with Enrichment and Dose -Expansion Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of GIM-122 as a Single Agent in Adult Subjects with Advanced Solid Malignancies.
General Inclusion Criteria:
In order to be eligible for this study, a subject must meet all of the following criteria:
1. Written informed consent must be obtained prior to any procedures.
2. Subject must be greater than or equal to 18 years of age
3. ECOG performance status 0-1
4. Must have the following laboratory values obtained less than or equal to 28 days prior to enrollment
a. Calculated creatinine clearance must be greater than or equal to 30 mL per min by Cockcroft-Gault
equation
b. Total bilirubin less than or equal to 1.5 × the upper limit of normal (ULN) or in the case of
known history of Gilberts syndrome, total bilirubin must be less than or equal to 3 × the ULN or
direct bilirubin less than or equal to 1.5 for× the ULN
c. Aspartate aminotransferase and alanine aminotransferase less than or equal to 2.5 × ULN, or
less than or equal to 5 × ULN for subjects with liver metastases
d. Hemoglobin greater than or equal to 9.0 g per dL. Note: Blood product transfusions can be allowed if Hb 8 g per dL - 9.0 g per dL during Screening.
e. Platelets greater than or equal to 100 × 109 cells per L
f. Absolute neutrophil count greater than or equal to 1.5 × 109 cells per L, without the use of
hematopoietic growth factors
g. Electrocardiogram (ECG) with QT corrected by Fredericia formula (QTcF) less than or equal to 470 ms in females and less than or equal to 450 ms in males (an average QTcF of the triplicate ECGs will be used to confirm eligibility)
5. Male subjects must agree to use a condom plus partner use of a contraceptive method with a failure rate of less than 1 percent per year, and refrain from donating sperm during the treatment period and for at least 90 days after the last dose of study drug. Male subjects with a pregnant partner must use a condom or remain abstinent from vaginal intercourse during the study and for 3 months following the birth. If the female partner plans to breastfeed, the male subject must discuss contraception with their physician prior to unprotected sex.
6. Female subjects of childbearing potential, defined as any female who has not been amenorrheic for 12 months without an alternative medical cause or is not surgically sterile, must agree to follow the contraceptive guidance (Section 10.14.4) during the treatment period and for at least 90 days after the last dose of the study drug.
Cancer-specific Inclusion Criteria
Subjects must meet all of the following criteria
1. Have a histologically or cytologically confirmed locally advanced or unresectable or metastatic solid tumor
2. Part B Dose Expansion, Indication F – NSCLC:
a. Have received no more than 2 prior lines of therapy for locally advanced, recurrent, or metastatic NSCLC. Treatment-naïve subjects who are not eligible for, do not tolerate, or refuse treatment with standard therapy may be enrolled with Sponsor approval.
b. Have not received prior immunotherapy for NSCLC (including, but not limited to, anti-PD-1, anti-PD-L1, or anti-cytotoxic t-lymphocyte associated protein 4 (CTLA4) therapies). Note: Inclusion criterion 14 (below) is not applicable to this cohort.
c. Must have PD-L1 expression status assessed from a commercially available assay. Subjects with unknown PD-L1 status can be enrolled but must provide archival or fresh tissue for retrospective PD-L1 assessment. Individual subjects without available tissue might be enrolled after Medical Monitor review.
d. Must be EGFR and BRAF wild-type. Subjects with known EGFR and/or BRAF mutations as well as subjects with ALK, RET, or ROS1 rearrangements are excluded. Subjects with unknown EGFR mutation status are excluded.
3. Part B Dose Expansion, Indication G – Cervical Cancer a. Have received no more than 2 prior lines of therapy for locally advanced, recurrent, or metastatic cervical cancer. Treatment-naïve subjects who are not eligible for, do not tolerate, or refuse treatment with standard therapy may be enrolled with Sponsor approval.
b. Have not received prior immunotherapy for cervical cancer (including, but not limited to, anti-PD-1, anti-PD-L1, or anti-CTLA4 therapies). Note: Inclusion criterion 14 (below) is not applicable to this cohort.
c. Must have HPV (HPV-DNA or p16-IHC) and PD-L1 expression (from a commercially available assay) status assessed from tissue. Subjects with unknown status can be enrolled but must provide archival or fresh tissue for retrospective HPV and PD-L1 assessment. Pap smears are acceptable for HPV testing. Individual subjects without available tissue might be enrolled after Medical Monitor review.
4. Have progressed or relapsed, are refractory, intolerant to, or declined treatment with standard therapy approved for the specific tumor type
5. Have at least 1 measurable lesion, as determined by RECIST v1.1, and a lesion (measurable or non-measurable) for biopsy
6. Consent to baseline biopsy or submission of archival tissue collected within the last 12 months. Fresh biopsies are mandatory if considered low risk (expected rate of major complications less than 0.5percent) unless approved by the Sponsor for enrollment without a fresh biopsy.
a. Subjects whose only site(s) of disease are considered medium or high risk for biopsy (defined as greater than 0.5percent risk of major complications) may be enrolled without submission of fresh tissue.
7. Had prior therapy with PD-1 or PD-L1 inhibitors, unless otherwise specified in indication-specific criteria. Other checkpoint inhibitors (ie. CTLA4, lymphocyte activation gene 3 (LAG-3)) are permitted, provided any toxicity attributed to these prior therapies did not lead to treatment discontinuation and resolved at the time of screening
ExclusionCriteria
Details
General Exclusion Criteria
For all cohorts, subjects are excluded from the study if any of the following criteria apply
1. Is enrolled in any other interventional clinical trial, starting within 4 weeks of the first dose of GIM-122 and throughout the duration of the study, or is receiving other therapy directed at their malignancy
2. Women who are pregnant or breastfeeding
3. History of any of the following less than or equal to 6 months prior to the first dose:
a. Congestive heart failure New York Heart Association Grade greater than or equal to 2
b. Unstable angina
c. Myocardial infarction
d. Unstable symptomatic ischemic heart disease
e. Uncontrolled hypertension despite appropriate medical therapy
f. Ongoing untreated symptomatic cardiac arrhythmias of greater than Grade 2
g. QTcF greater than 470 ms on screening ECG or congenital long QT syndrome
h. Pulmonary embolism
i. Symptomatic cerebrovascular events
j. Any other serious cardiac condition (eg. significant pericardial effusion or restrictive cardiomyopathy); chronic atrial fibrillation on stable anticoagulant therapy is allowed
k. Active and clinically significant bacterial, fungal, or viral infection, including known Hepatitis B or C virus (HBV or HCV, testing not required), or human immunodeficiency virus or acute or chronic infection of Coronavirus Disease 2019 (COVID-19) as determined by polymerase chain reaction or antigen test
Note: subjects whose HIV, HBV, or HCV infection is controlled by antiviral therapy should not be excluded.
4. Any contraindications to the imaging assessments or other study procedures that subjects will undergo 5. Any medical or social condition that, in the opinion of the investigator, might place a subject at an increased risk, affect compliance, or confound safety or other clinical study data interpretation Cancer-specific Exclusion Criteria
For all cohorts, subjects are excluded from the study if any of the following criteria apply:
1. Current second malignancy at other sites
a. Exceptions: non-melanomatous skin cancer, adequately treated in situ carcinoma (eg. cervical), or indolent prostate cancer under observation. A history of other malignancies is allowed as long as the subject is free of recurrence for greater than or equal to 3 years.
2. Leptomeningeal disease
3. Spinal cord compression
4. Symptomatic or new or enlarging central nervous system (CNS) metastases
a. Asymptomatic CNS disease must be treated and stable on imaging by magnetic resonance imaging scan within 28 days of study treatment in order to be eligible for this study.
Treatment-specific Exclusion Criteria
1. Subject has ongoing toxicity > Grade 1 from prior therapy according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (Grade 2 sensory neuropathy and Grade 2 alopecia are allowed).
2. Has undergone a major surgery (excluding minor procedures, e.g., placement of vascular access) < 1 month prior to administration of GIM-122.
3. Part A Enrichment: Has received more than 3 prior lines of anticancer treatment in the metastatic setting. For subjects with CRPC, androgen deprivation therapies will not be counted as separate lines of anticancer treatment in determining eligibility per Section 8.2.3 Criterion 3.
4. Part B Dose Expansion, Indication F – NSCLC: Subjects with known EGFR and/or BRAF mutations as well as subjects with ALK, RET, or ROS1 rearrangements are excluded. Subjects with unknown EGFR mutation status are excluded.
5. Has received radiation therapy within 2 weeks prior to administration of GIM-122.
a. Exception: limited (e.g., pain palliation) radiation therapy is allowed prior to and during the study treatment as long as there are no acute toxicities, and the subject has measurable disease outside the radiation field.
6. Has received systemic anticancer therapy within 2 weeks of the first dose of GIM-122. For cytotoxic agents that have a major delayed toxicity (e.g., mitomycin C and nitrosourea), 4 weeks is indicated as a washout period.
7. Prior treatment with other immune modulating agents within less than 4 weeks prior to the first dose of GIM-122. Examples of immune modulating agents include anti- CTLA-4, PD-L1, 4-IBB (CD137), OX-40, LAG-3, therapeutic vaccines, or cytokine treatments.
8. Has a diagnosis of immunodeficiency, either primary or acquired
9. Has received treatment with systemic steroids or any form of immunosuppressive therapy (greater than or equal to 10 mg per day prednisone equivalent) within 14 days prior to administration of GIM-122.
a. Exception: inhaled or topical steroids and adrenal replacement doses are permitted in the absence of active autoimmune disease.
10. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
a. Exception: subjects with Type 1 diabetes (if stable, well-controlled, and not brittle), vitiligo, hypothyroid or hyperthyroid disease, or autoimmune alopecia are permitted if the condition is stable and does not require immunosuppressive treatment.
11. Has a known severe intolerance to or hypersensitivity reactions to monoclonal antibodies, Fc-bearing proteins (eg. soluble receptors or other Fc fusion proteins), or IV immunoglobulin preparations, prior history of human anti-human antibody
Response, known allergy to any of the study medications, or excipients in the various formulations of any agent.
12. Has received a live vaccine within 30 days of study initiation (inactivated vaccines are allowed; seasonal vaccines should be up to date greater than 30 days prior to administration of GIM-122). Severe acute respiratory syndrome-associated coronavirus vaccines authorized for use for active immunization to prevent COVID-19 are allowed unless the vaccine is live or live attenuated) and must be given in accordance with the prevailing immunization guidelines.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To assess the antitumor activity of GIM-122 as a single agent in subjects with PD-1/
PD-L1 refractory/resistant advanced solid tumor malignancies.
Week 1-3, 4-6, 7-9, onward up to 12 months.
Secondary Outcome
Outcome
TimePoints
To assess safety and tolerability
To characterize the PK profile of GIM-122
To assess the emergence and persistence of anti-drug antibodies (ADA) and the impact on GIM-122 exposure
To assess the change from baseline in tumor tissue biomarkers as potential predictors of efficacy of GIM-122
Week 1-3, 4-6, 7-9, onward up to 12 months.
Target Sample Size
Total Sample Size="110" Sample Size from India="40" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
GIM-122, a first-in-class,
humanized immunoglobulin G1 kappa dual functioning monoclonal antibody (DFA),
targets an epitope on programmed cell death protein-1 (PD-1) that is conserved
across species (human, monkey, dog, rat, and mouse). PD-1, an important immune
inhibitory receptor, is critical for the maintenance of central and peripheral
T cell tolerance (Waldman et al,2020). Georgiamune has discovered that PD-1 is a
dual-functioning receptor, able to deliver inhibitory, as well as stimulatory
signals, in T cells (manuscript in preparation). GIM-122 shuts down the
inhibitory immune checkpoint signaling and simultaneously delivers an additional
activating signal in antigen-primed T cells.