This study is a single arm, multi-center, open label phase Ib/II study of SC0245 and Irinotecan combination therapy in subjects with extensive-stage small cell lung cancer (ES-SCLC) as a second therapy. This study will have three parts, phase 1 dose escalation (Part 1), phase 1 dose expansion (Part 2), and phase 2 combination therapy (Part 3).
This study will have three parts, phase 1 dose escalation (Part 1), phase 1 dose expansion (Part 2), and phase 2 combination therapy (Part 3). Subjects will receive SC0245 and Irinotecan combination therapy. The study is composed of 67 subjects. Irinotecan 80mg/m2 via IV administered for every 4 weeks (fixed dosing) in Day 1 Day8 and Day 15 of each cycle, and SC0245 administered with a 3-day on and 4-day off schedule in Day 1 Day8 and Day 15 of each cycle. One cycle is consisted of 28 days. Study treatment will be continued until objective disease progression (unless other criteria for treatment discontinuation are met). Tumor evaluation using CT or MRI by RECIST 1.1 every 8weeks(±1week) until objective disease progression. RECIST 1.1 scans will be analyzed by the investigator on site. If a subject discontinues study treatment prior to disease progression, they should continue to be assessed using RECIST 1.1 until disease progression and then followed up for survival. Primary Objective: Part 1 (phase 1 dose escalation): To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of SC0245 in combination with irinotecan in patients with advanced solid tumors. Part 2 (phase 1 dose expansion): To evaluate the safety and tolerability of SC0245 in combination with irinotecan in patients with relapsed extensive-stage small cell lung cancer (ES-SCLC). Part 3(phase 2 combination therapy): To evaluate the preliminary anti-tumor activity of SC0245 in combination with irinotecan in patients with relapsed extensive-stage small cell lung cancer (ES-SCLC). Secondary Objective: Part 1 (phase 1 dose escalation): To characterize the PK profile and the preliminary anti-tumor activity. Part 2 (phase 1 dose expansion): To characterize the PK profile, safety and tolerability and the preliminary anti-tumor activity in patients with relapsed extensive-stage small cell lung cancer (ES-SCLC). Part 3(phase 2 combination therapy): To characterize the safety and tolerability and the preliminary anti-tumor activity in patients with relapsed extensive-stage small cell lung cancer (ES-SCLC).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
67
SC0245 Quaque Die(QD) administered with a 3-day on and 4-day off schedule in Day 1 Day8 and Day 15 of each cycle. One cycle is consisted of 28 days.
Irinotecan 80mg/m\^2 via IV administered for every 4 weeks (fixed dosing) in Day 1 Day8 and Day 15 of each cycle. One cycle is consisted of 28 days.
Shanghai Chest Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGPart 1 (phase 1 dose escalation):Maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of SC0245 and irinotecan
MTD Will be defined as the highest dose level at which =\< 30% patients experience dose limiting toxicity. Dose-limiting toxicity as described in the protocol that is not related to disease progression, intercurrent illness or concomitant medications and that, despite optional therapeutic intervention, meets protocol-defined criteria. The RP2D will be determined based on MTD and the feasibility of the administration.
Time frame: Up to 28 days
Part 2 (phase 1 dose expansion):Safety and tolerability in terms of adverse events
Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters.
Time frame: From the first dose of study treatment until 30 days after the last dose, up to approximately 24 months
Part 3(phase 2 combination therapy):Objective response rate (ORR)
Defined as the percentage of participants having a CR or PR based on investigator assessment per RECIST v1.1.
Time frame: Up to 24 months.
Disease Control Rate (DCR) Based on RECIST v1.1
Defined as the percentage of participants having CR, PR, or stable disease (SD) based on investigator assessment per RECIST v1.1.
Time frame: Assessed every 8 weeks, up to 24 months.
Duration of Response (DoR) Based on RECIST v1.1
Defined as the time from the earliest date of disease response (CR or PR) until earliest date of disease progression or death due to any cause.
Time frame: Assessed every 8 weeks, up to 24 months.
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Progression-free Survival (PFS) Based on RECIST v1.1
Defined as the time from the start of combination therapy until the earliest date of disease progression or death due to any cause.
Time frame: Assessed every 8 weeks, up to 24 months.
Overall Survival (OS)
Defined as the time from the start of combination therapy until death due to any cause.
Time frame: At 1 year and 2 years.
Incidence of adverse events of SC0245 and irinotecan
Will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. A toxicity will be considered to be an adverse event that is possibly, probably or definitely related to treatment. The maximum grade of toxicity for each category of interest will be recorded for each patient, and the summary results will be tabulated by category, grade, and dose level. Serious (\>= grade 3) toxicities will be described on a patient-by-patient basis and will include any relevant baseline data.
Time frame: From the first dose of study treatment until 30 days after the last dose, up to approximately 24 months
Maximum observed blood concentration (Cmax) of SC0245
Defined as assessments for measuring maximum blood concentration of SC0245
Time frame: Pre-dose up to approximately 6 months
AUC Area under the Plasma Concentration versus Time Curve (AUC) of SC0245
Defined as assessments for evaluating the Area Under the Concentration-Time Curve (AUC)
Time frame: Pre-dose up to approximately 6 months
Elimination half-life (t1/2) of SC0245
Defined as the time required for half of the drug SC0245 to be eliminated from the blood.
Time frame: Pre-dose up to approximately 6 months