A Study to Assess Safety, Efficacy, Immunogenicity, PK of GC1118 With Combination Chemotherapy

Study Overview
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Brief Summary
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The purpose of the study is to assess the safety and tolerability of GC1118 in combination with irinotecan or FOLFIRI in order to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D)

Detailed Description
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A Phse 1b/2a, dose-finding, open-label, prospective study This study consists of the Phase 1b part designed to determine the MTD and RP2D of GC1118 when administered in combination with irinotecan or FOLFIRI to patients with recurrent metastatic solid tumors and the Phase 2a part designed to assess the efficacy of GC1118 in combination with FOLFIRI as second-line therapy for recurrent/metastatic colorectal cancer

Official Title
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Phase 1b/2a Study of GC1118 in Combination With Irinotecan or FOLFIRI in Patients With Recurrent/Metastatic Solid Tumor

Conditions
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Metastatic Colorectal Cancer, Solid Tumor

Intervention / Treatment
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* Drug: irinotecan
* Drug: FOLFIRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Phase 1b: Histologically or cytologically confirmed recurrent/metastatic solid cancer patients with no available standard treatment and be expected to have the anti-tumor effect with combination of GC1118 and irinotecan or GC1118 and FOLFIRI by investigator's judgement Phase 2a: Historically or cytologically confirmed, 1) EGFR-positive, KRAS/NRAS and BRAF wild type recurrent/metastatic colorectal cancer patients who failed first line chemo or targeted therapies (fluoropyrimidine-based or oxaliplatin containing chemotherapy) or whose disease were progressed within 6 months after the last dose of above mentioned treatments; Disease progression during treatment or within 6 months after completion of adjuvant/neoadjuvant chemotherapy is also considered as first line treatment failure 2) Medically documented non-HER2 overexpression (HER2 3+ or HER2+/FISH+) and EGFR 2+ or 3+ expressing recurrent/metastatic gastric cancer patients who failed (radiologically progressed) second line chemo or targeted therapies Male of female, 19 years of age or older ECOS PS 0 or 1 Life expectancy of 3 months or longer Phase 2a: Presence of at least one measurable lesion according to the RECIST criteria v1.1 Phase 2a: Demonstration of each cohort requirements including EGFR positive, KRAS/NRAS and BRAF wild type, EGFR 2+ or 3+ expression, and etc. Adequate bone marrow function, renal function, and hepatic function All AEs caused by previous anticancer therapies, including surgery, chemotherapy, and radiation therapy,have recovered to CTCAE grade 1 or below (except alopecia) Exclusion Criteria: Any of the following medical histories 1) Major surgery, open biopsy, or significant traumatic injury within 4 weeks prior to the first investigational products administration or adverse events are not resolved from such procedure or injury 2) Other malignancies (exception; any of the following status are eligible) i. Disease free for 3 years or completely resected non-melanoma skin cancer ii. Successfully treated in carcinoma in situ (CIS) iii. Ta, CIS, or T1a staged superficial bladder cancer which is completely cured iv. Papillary thyroid cancer which is not being progressed without ongoing treatment v. Prostate cancer which is surgically or medically cured and is not likely to recur within 2 years Any of the following concurrent disease 1) Known brain metastasis 2) Active infection requiring systemic anti-microbial therapy 3) Human immunodeficiency virus infection or active hepatitis B or C 4) Chronic inflammatory bowel disease 5) Clinically significant interstitial lung disease or pulmonary fibrosis 6) Clinically significant hepatic disease including decompensated liver cirrhosis, etc Any of the following medication histories 1) Phase 2a recurrent/metastatic colorectal cancer: Treated with irinotecan containing regimen as first line treatment for recurrent/metastatic cancer 2) Phase 2a: Prior EGFR targeting antibody therapy 3) Received chemotherapy, immunotherapy, hormone therapy, radiotherapy within 3 weeks (within 6 weeks in case of nitrosourea or mitomycin-c) prior to first investigational products administration (In phase 2, radiotherapy within 3 weeks is not restricted unless the site is measurable lesion) 4) Ongoing or requiring the prohibited medications including immunotherapy, chemotherapy, hormone therapy, or etc. 5) Received other investigational drugs with 4 weeks prior to this investigational products adminstration Medically or psychologically inappropriate conditions for study participation by investigator's judgment Contraindication for FOLFIRI (or irinotecan) therapy Pregnant, possibly pregnant, or lactating women (Women of child bearing potential must test negative for pregnancy within 3 days prior to Cycle1 Day1 Refusal to use the following appropriate contraceptives during the clinical study period and for 6 months after the last adminstration of investigational products 1) Implanted intrauterine device or intrauterine system 2) Double barrier methods (Both of condom (for mate) and diaphragm, vaginal sponge, or cervical cap (for female) should be used with spermicide) 3) Surgical sterilization (vasectomy, tubal ligation, etc.) Any other inappropriate conditions for study participation at investigator's discretion

Ages Eligible for Study
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Minimum Age: 19 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: GC1118 combination with irinotecan<br>GC1118 weekly(3mg or 4mg) + irinotecan 180mg/m2 biweekly dosing | Drug: irinotecan<br>* GC1118 combination with irinotecan<br>|
| Experimental: GC1118 combination with FOLFIRI<br>GC1118 weekly(3mg or 4mg) + FOLFIRI biweekly dosing | Drug: FOLFIRI<br>* GC1118 combination with FOLFIRI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limited Toxicity (DLT) | Profile of DLT | through study completion, approximately 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response according to RECIST 1.1 criteria | best overall response (BOR) | before start of treatment, every 6 weeks for the duration of treatment, up to approximately 2 years. | 
| Tumor response according to RECIST 1.1 criteria | objective response rate (ORR) | before start of treatment, every 6 weeks for the duration of treatment, up to approximately 2 years. | 
| Pharmacokinetics of GC1118 | area under th curve (AUC) | through study completion, approximately 5 months | 
| Pharmacokinetics of GC1118 | half life | through study completion, approximately 5 months | 
| Pharmacokinetics of GC1118 | clearance | through study completion, approximately 5 months | 
| Pharmacokinetics of GC1118 | peak serum concentration (Cmax) | through study completion, approximately 5 months | 
| Immunogenicity of GC1118 | occurrence frequency of anti-drug antibody | every odd number cycles through treatment period, 28 days after the last treatment |