Advanced Solid Tumors, Non-Small Cell Lung Cancer
Conditions
Keywords
c-Met, CKD-703, Advanced Solid Tumors, Non-Small Cell Lung Cancer
Brief summary
This is a Phase 1/2a open-label multicenter study to evaluate the safety, efficacy, and pharmacokinetics of CKD-703 in Advanced c-Met Expressing Solid Tumors, and in MET-Amplified and c-Met Overexpressing Non-Small Cell Lung Cancer. CKD-703 is composed of a c-Met-targeting monoclonal antibody (mAb) coupled to a cytotoxic payload consisting of the anti-microtubule drug monomethyl auristatin E (MMAE); thus, CKD-703 is a novel ADC offering a highly targeted approach with potential improvement of efficacy while reducing off-target effects for patients with NSCLC and other cancers.
Interventions
DRUGCKD-703
Intravenous (IV) Infusion
Sponsors
Chong Kun Dang Pharmaceutical
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females ≥ 19-year-old * Part 1 : Solid tumors including NSCLC for which standard therapy has failed or was not tolerated, and no other effective therapy exists * Part 2 : Histologically or cytologically documented c-Met overexpressing nonsquamous NSCLC having failed at least 1 line of SoC therapy (platinum-based chemotherapy and/or immune checkpoint inhibitor). * Part 3 : Histologically or cytologically documented c-Met expressing solid tumors for which standard therapy has failed or was not tolerated. * In all parts of the study, subjects with NSCLC with documented actionable genetic alterations must have failed at least 1 line of country-level approved targeted therapies * Life expectancy ≥ 12 weeks as judged by the Investigator * Documented progressive and measurable disease as defined by RECIST 1.1 * ECOG Performance Status 0 or 1
Exclusion criteria
* Subject has received radiation therapy to the lung \< 6 months prior to the first dose of study drug * Prior radiotherapy to ≥ 25% of bone marrow * Anticancer systemic therapy such as immunotherapy, biologic, cytotoxic chemotherapy, or any investigational therapy (including cell therapy or gene therapy) within a period of 28 days prior to the first dose of study drug. Any anticancer therapy small molecule (eg. kinase inhibitor) or herbal therapy within 14 days prior to the first dose of study drug * Prior c-Met-targeted antibody therapy or any MMAE-containing ADC (prior c-Met targeting small molecules are allowed) * Use of strong P-gp and/or CYP3A4/5 inducers within 21 days prior or strong P-gp and/or CYP3A4/5 inhibitors within 14 days prior to the first dose of study drug * Use of sensitive CYP3A4/5 substrate within 3 days or 5 times half-life prior to the first dose of study drug. * Evidence of pulmonary fibrosis on screening imaging assessment or any history of pneumonitis that required treatment with systemic steroids within 12 months of the planned first dose of the study drug * History of drug induced interstitial lung disease * Prior or active ocular or corneal disease based on ophthalmic evaluation (slit lamp and visual acuity) * Prior Grade 3 neuropathy or chronic Grade 2 neuropathy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of patients with dose limiting toxicity (DLT) | first 21-day period of therapy | Collect all adverse events at each visit |
| Part 2 and Part 3: Object Response Rate (ORR) | Up to 24 months | ORR defined as the proportion of subjects with a best Investigator-assessed confirmed objective response of CR or PR according to RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All parts : Treatment-Emergent Adverse Events (TEAE) | Up to 24 months | Incidence of SAEs, SUSARs, TEAEs, and AESI |
| All parts : Immunogenicity (ADA) | Up to 24 months | Blood samples were collected and assessed by validated immunoassays for immunogenicity of CKD-703, including the incidence of anti-drug antibodies (ADA) |
| All parts : Immunogenicity (NAb) | Up to 24 months | Blood samples were collected and assessed by validated immunoassays for immunogenicity of CKD-703, including the incidence of neutralizing antibodies (NAb) |
| Part 1 and Part 2 : Pharmacokinetic parameter | Up to 24 months | CKD-703 (conjugated antibody) |
| Part 1 and Part 3 : Best Overall Response (BOR) | Up to 24 months | Defined as best objective response of CR, PR, SD, PD, or not evaluable at the end of treatment |
| All parts : Duration of Response (DoR) | Up to 24 months | Defined as the time from the date of first documented CR or PR until the date of documented progression or death |
| Part 2 and Part 3 : Progression-Free Survival (PFS) | Up to 24 months | Defined as the time from the date of first dose to the date of progression or death |
| Part 2 and Part 3 : Overall Survival (OS) | Up to 24 months | Defined as the time from first dose to the date of death |
Countries
United States
Outcome results
None listed