A Study of hSTC810 in Combination With Paclitaxel in Relapsed or Refractory Extensive Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this clinical study is to assess the safety and efficacy of hSTC810 and paclitaxel combination therapy in patients with relapsed or refractory extensive stage small cell lung cancer.

Detailed Description
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The study will be conducted in 2 parts. Phase Ib will evaluate the safety of the combination of hSTC810 with a standard dose of paclitaxel using a 3+3 dose escalation design. Phase II will evaluate the efficacy of hSTC810 + paclitaxel combination therapy using a Simon 2-stage method.

Official Title
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A Phase Ib/II Study of hSTC810 in Combination With Paclitaxel in Relapsed or Refractory Extensive Stage Small Cell Lung Cancer

Conditions
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Extensive Stage Small Cell Lung Cancer

Intervention / Treatment
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* Drug: hSTC810 400 mg + Paclitaxel
* Drug: hSTC810 800 mg + Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and sign an informed consent form Male or female ≥ 18 years of age Histologically or cytologically confirmed SCLC R/R ES-SCLC on or after platinum-based chemotherapy for SCLC with documented disease progression At least 1 measurable lesion as defined by RECIST 1.1 Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 or 1 Life expectancy of at least 3 months Adequate organ function as described in the protocol For female or male patients with reproductive potential: Agree to use contraception throughout the study and at least 5 months after the last dose. Exclusion Criteria: Known active leptomeningeal disease (carcinomatous meningitis) Known active and uncontrolled central nervous system (CNS) metastases Treatment with immunotherapy, chemotherapy, targeted small molecule therapy, or any other investigational agent < 14 days prior to initiation of study treatment Treatment with radiation therapy < 14 days prior to initiation of study treatment Major surgery < 21 days prior to initiation of study treatment Received live vaccine < 30 days prior to initiation of study treatment, including intranasal influenza vaccine History of another primary malignancy with protocol-defined exceptions Active or history of autoimmune disease requiring systemic treatment Receiving high doses of steroids or other immunosuppressive medications Active hepatitis B or C infection Active or history of non-infectious pneumonitis requiring treatment with steroids Active uncontrolled viral, fungal, or bacterial infection including tuberculosis Pregnant or breastfeeding female patients History of severe hypersensitivity reaction to a monoclonal antibody treatment History of severe hypersensitivity reaction or ≥ Grade 3 adverse event (AE) to paclitaxel treatment History of cerebral vascular event, unstable angina, myocardial infarction, or cardiac symptoms within 6 months prior to screening QT Corrected for Fridericia's method (QTcF) > 470 ms at screening Lack of resolution of any toxicity to max Grade 1 (except alopecia) Active or history of any condition, therapy, or lab abnormality that may interfere with the patient participation for the full duration of the study Known psychiatric or substance use disorder Positive Coronavirus disease 2019 (COVID-19) test at screening

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: hSTC810 400 mg + Paclitaxel<br>hSTC810 400 mg will be administered with a standard dose of paclitaxel | Drug: hSTC810 400 mg + Paclitaxel<br>* hSTC810 400 mg and paclitaxel 175 mg/m2 will be administered as an intravenous (IV) infusion Paclitaxel: 175 mg/m2 will be administered as an IV infusion<br>|
| Experimental: hSTC810 800 mg + Paclitaxel<br>hSTC810 800 mg will be administered with a standard dose of paclitaxel | Drug: hSTC810 800 mg + Paclitaxel<br>* hSTC810 800 mg and paclitaxel 175 mg/m2 will be administered as an IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Percentage of patients with confirmed Confirmed Response (CR) or Partial Response (PR) as defined by RECIST 1.1 at 3 months | 3 months | 
| Progression Free Survival (PFS) rate | Proportion of patients without documented progression of disease and alive at 6 months | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Incidence, causality, and nature of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | Up to 4 years | 
| Overall Response Rate (ORR) | Investigator assessed ORR defined by RECIST 1.1 | Up to 4 years | 
| Duration of Response (DoR) | Time from the date of first documented CR or PR until the date of documented progression or death | Up to 4 years | 
| Progression Free Survival (PFS) | Time from first dose until the date of objective disease progression or death | Up to 4 years | 
| Clinical Benefit Rate (CBR) | Percentage of evaluable patients with CR, PR, or Stable Disease (SD) lasting ≥ 24 weeks | Up to 4 years | 
| Overall Survival (OS) | Time from first dose of study drug until the date of death | Up to 4 years | 
| Overall Survival (OS) rate | Proportion of patients alive at 12 months after the first dose of study drug | 12 months | 
| Maximum plasma concentration (Cmax) | Maximum plasma concentration of hSTC810 to evaluate PK parameters | Up to 21 days | 
| Area under the concentration-time curve from 0 to 21 days (AUC0-21) | AUC from 0 to 21 days to evaluate PK parameters | Up to 21 days | 
| Area under the concentration-time curve extrapolated from 0 to infinity (AUCo-inf) | AUC from time 0 to infinity to evaluate total drug exposure over time | Up to 21 days | 
| Incidence of anti-drug antibodies (ADA) | Number and percentage of patients with positive ADAs | Up to 4 years |