Study of NIB101 in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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NIB101-01 study is an open-label, non-randomized Phase 1 study in participants with GM2 positive advanced solid tumor, who failed to available standard of cares to evaluate the safety and tolerability of NIB101.

Detailed Description
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The screening begins by signing the informed consent form and determining the participant's initial eligibility. Alternatively, in advance, the prescreening enables participants to confirm GM2 expression using the archived samples by signing the prescreening ICF prior to the screening. After the consent is obtained and the eligibility of participants is confirmed, the participant will undergo apheresis. Lymphodepleting chemotherapy will be administered prior to NIB101 infusion. After manufacturing of NIB101, participants will receive a single dose of NIB101 intravenously on Day 0 and be followed for safety and efficacy.

Official Title
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An Open-Label Non-Randomized Phase 1 Dose Escalation and Dose Expansion Study of NIB101 in Participants With Advanced Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Biological: NIB101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant with histologically or cytologically confirmed solid tumor. Participant who failed or are intolerable to available standard of cares (regardless of the number of prior lines of therapy) at the investigator's discretion. Participant whose tumor tissues express GM2 membrane as determined by immunohistochemistry. Participant who has measurable lesions. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Life expectancy >=12 weeks from the signing screening ICF. Participant with adequate organ functions. Participant who can undergo apheresis at the investigator's discretion. Participant must agree to use adequate contraception methods Participant who is willing to sign a written informed consent. Exclusion Criteria: Active brain metastasis on the screening MRI (in case of MRI contradiction, CT is acceptable) Participant with an active, known or suspected autoimmune disease requiring immune suppressive agents other than hormonal replacement therapy. Prior malignancy (other than targeted GM2 positive malignancy) within the previous 3 years the signing screening ICF. Suspected malignant lymphoma or leukemia Participant with known or suspected interstitial pneumonia Active infections requiring treatments Participant with an active, known or suspected gangliosidosis. Other concurrent serious diseases that may interfere with planned study intervention per investigator's discretion. Prior treatment with engineered T-cell therapy/gene therapy. Prior treatment with any GM2, Interleukin-7 (IL-7) or Chemokine (C-C motif) ligand 19 (CCL19) targeted therapy. Participant with a condition requiring systemic treatment with either corticosteroids (>= 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to apheresis. Inhaled or topical steroids, and adrenal replacement steroid doses <10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Participant with adverse events due to prior therapy have not recovered to grade 1 or baseline, except for non-clinically significant adverse events at the investigator's discretion such as alopecia. Anti-neoplasm treatment within 14 days prior to apheresis Radiation therapy within 14 days prior to apheresis Participant currently requiring ganciclovir, valganciclovir, and so on (the drug that provides HSV-TK substrate) treatment. Participants currently receiving prophylaxis treatment can be enrolled if the prophylaxis treatment is completed before apheresis. Major surgery within 4 weeks prior to screening informed consent. Prior treatment with any investigational study drug/investigational study cell and gene therapies within 28 days before signing screening ICF. Positive human immunodeficiency virus (HIV) and/or Human T-cell leukemia virus-1 (HTLV-1) antibody test on the screening prior to apheresis. Positive Hepatitis B surface (HBs) antigen or Hepatitis C virus (HCV) antibody test on the screening prior to apheresis. Participant who has positive HBs antibody or Hepatitis B core (HBc) antibody can be enrolled if Hepatitis B virus (HBV)-DNA is undetectable. Any symptoms of suspected syphilis Pregnant or breastfeeding History of allergy or hypersensitivity to components of NIB101 or materials used for manufacturing NIB101. Hypersensitivity or contraindicated to study intervention components.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NIB101 Dose Level 1<br>1 x 10^7 cells/body as chimeric antigen receptor (CAR) positive viable cells will be administered intravenously on Day 0. | Biological: NIB101<br>* NIB101<br>|
| Experimental: NIB101 Dose Level 2<br>1 x 10^8 cells/body as CAR positive viable cells will be administered intravenously on Day 0. | Biological: NIB101<br>* NIB101<br>|
| Experimental: NIB101 Expansion Cohort<br>Recommended dose determined on dose escalation phase will be administered intravenously on Day 0. | Biological: NIB101<br>* NIB101<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities | Specific adverse events defined in the protocol and related to NIB101 infusion | 28 days after NIB101 infusion | 
| Adverse Events | Number of participants with adverse events | 2 years from NIB101 infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response | Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD) determined by the investigator per RECIST version 1.1 or modified RECIST | 2 years from NIB101 infusion | 
| Overall Response Rate | Percentage of subjects who achieved PR or better | 2 years from NIB101 infusion | 
| Disease Control Rate | Percentage of subjects who achieved SD or better | 2 years from NIB101 infusion | 
| Duration of Response | Time from first documentation of response (PR or better) to first documentation of disease progression or death from any cause | 2 years from NIB101 infusion | 
| Time To Response | Time from NIB101 infusion to the initial documented response (PR or better) | 2 years from NIB101 infusion | 
| Progression Free Survival | Time from NIB101 infusion to the date of disease progression or death from any cause. | 2 years from NIB101 infusion | 
| Overall Survival | Time from NIB101 infusion to time of death due to any cause | 2 years from NIB101 infusion | 
| Pharmacokinetics (Cmax) | Maximum peak of NIB101 | 2 years from NIB101 infusion | 
| Pharmacokinetics (Tmax) | Time to maximum peak of NIB101 | 2 years from NIB101 infusion | 
| Pharmacokinetics (T1/2) | Half life of NIB101 | 2 years from NIB101 infusion | 
| Pharmacokinetics (Clast) | Concentration of last quantified NIB101 | 2 years from NIB101 infusion | 
| Pharmacokinetics (Tlast) | Time of Clast observed | 2 years from NIB101 infusion | 
| Pharmacokinetics (AUC) | Area under the curve of NIB101 | 2 years from NIB101 infusion | 
| Immunogenicity | Evaluation of an anti-CAR antibody response | 2 years from NIB101 infusion | 
| Replication Competent Retrovirus (RCR) | Number of cases of positive RCR | 2 years from NIB101 infusion |