Combination therapy of SC0245 and Irinotecan for relapsed extensive-stage small cell lung cancer

A Phase Ib/II , Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-Tumor Effects of SC0245 in Combination With Irinotecan in Patients With ES-SCLC

This study is testing a new combination of two drugs, SC0245 and Irinotecan, to see if it can help people with relapsed extensive-stage small cell lung cancer who have run out of other treatment options.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 67 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Biocity Biopharmaceutics Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05731518 on ClinicalTrials.gov

What this trial studies

This clinical trial is a single-arm, multi-center, open-label study evaluating the combination of SC0245 and Irinotecan in patients with relapsed extensive-stage small cell lung cancer (ES-SCLC). The study consists of three parts: a phase 1 dose escalation to determine the maximum tolerated dose, a phase 1 dose expansion to assess safety and tolerability, and a phase 2 component to evaluate the preliminary anti-tumor activity of the combination therapy. Participants will receive treatment in cycles, with tumor evaluations conducted every eight weeks until disease progression. The study aims to provide a new therapeutic option for patients who have exhausted standard treatment options.

Who should consider this trial

Good fit: Ideal candidates include adults with relapsed extensive-stage small cell lung cancer who have previously received platinum-based chemotherapy.

Not a fit: Patients with early-stage small cell lung cancer or those who have not received prior chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a new effective option for patients with relapsed extensive-stage small cell lung cancer.

How similar studies have performed: While similar combination therapies have been explored, this specific combination of SC0245 and Irinotecan is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Histologically or cytologically confirmed solid tumor.
2. Phase 1b dose-escalation stage: patients with advanced solid tumors, who have received standard treatment, for who no standard treatment exists, who are not suitable for standard treatment at the current situation, or who could not tolerate standard treatment.

   Phase 1b dose-expansion stage and phase 2: patients with ES-SCLC who have received first-line platinum-based regimen chemotherapy with or without immunotherapy or intolerance to such therapy.
3. Measurable lesions according to RECIST version 1.1 (only applicable for phase 1b dose-expansion and Phase 2).
4. Male or non-pregnant, non-lactating female patients age ≥18 years on day of signing the informed consent.
5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
6. Life expectancy ≥ 3 months.
7. Adequate organ function .
8. Females of child-bearing potential (nonlactating) must have a negative blood pregnancy test within 7 days before enrollment, and must agree to use a medically effective contraception from the time they provided the informed consent until at least 6 months (or at least 180 days) after the last dose of study drug, unless surgical sterilization or menopause for more than 1 year. Patients who are sexually active men with a female partner of child-bearing potential must agree to use adequate contraception from the time they provided informed consent until at least 6 months after the last dose.
9. Subjects voluntarily participate in this study and sign the informed consent form.

Exclusion Criteria:

1. Received chemotherapy within 3 weeks before first dose of study drug (6 weeks for nitrosoureas or mitomycin C)
2. Received wide field radiotherapy within 4 weeks before first dose of study drug (previous palliative radiation therapy for metastatic disease is permitted if it has been completed at least 1 week before first dose of study drug and related toxicity has recovered to ≤ grade 1)
3. Received any monoclonal antibody, radioimmunoconjugate or antibody-drug conjugates (ADC) within 5 half-lives or 4 weeks (whichever is shorter) before first dose.
4. Received any other type of anti-tumor therapy including other investigational drugs or treatments not listed above within 4 weeks before first dose of study drug.
5. Had major organ surgery, except diagnostic biopsy, or significant trauma within 4 weeks, or not fully recovered from surgery within 4 weeks before first dose of study drug.
6. Received traditional Chinese herbal medicines with anti-tumor indications within 2 weeks before first dose of study drug.
7. Previously received any Ataxia-Telangiectasia and Rad3 Related（ATR）inhibitor.
8. Continuous toxicities due to prior treatments that do not recover to ≤ Grade 1 severity per NCI CTCAE v5.0 except for clinically non-significant events judged by the Investigator (e.g., alopecia, grade 2 peripheral neurotoxicity, stable hypothyroidism with hormone replacement therapy, etc.)
9. Allergy to any component of the SC0245 tablets and irinotecan injection or who meet contraindications to irinotecan. In addition, the prohibited concomitant drugs in irinotecan label should be avoided.
10. Crigler-Najjar syndrome (Type I and II) or UGT1A1 mutation that increases irinotecan toxicity (Gilbert's syndrome).
11. Central nervous system (CNS) metastases meeting any of the following condition:

    * Presence of new or progressive lesions in brain by imaging within 4 weeks prior to first dose of study drug
    * Presence of symptoms of CNS metastasis
    * Received corticosteroids, radiotherapy, or dehydration drugs within 1 week to control symptoms of CNS metastasis (except for patients who completed radiotherapy for brain metastases, no use of cortisol and dehydration drugs without neurologic symptoms for more than 1 week, and brain metastases are in a stable state or have shrinkage during follow-up visit at least 2 weeks later, which need to be confirmed before first dose of study drug)
    * Carcinomatous meningitis
    * Brain stem (midbrain, pons, medulla oblongata) and spinal cord metastases
12. Active infections that require systematic treatment
13. Severe cardiovascular disorder, who meet any of the following conditions:

    * corrected QT interval(QTc)\> 470 ms
    * Severe cardiac rhythm or conduction abnormalities, including but not limited to complete left bundle branch block, atrioventricular block of degree II or above, rapid ventricular tachycardia (including frequent premature ventricular contractions), torsades de pointes.
    * Any risk factors that increase the prolongation of the QTc interval, such as uncorrectable hypokalemia, genetic long QT syndrome, taking medications that prolong the QTc interval (mainly antiarrhythmic drugs of Class Ia, Ic, or III)
    * Congestive heart failure (New York Heart Association Class≥3), or a left ventricular ejection fraction of less than 50%
    * Clinically uncontrolled hypertension, defined as systolic blood pressure (SBP) ≥ 160 mmHg and diastolic blood pressure (DBP) ≥ 100 mmHg after medication.
    * Acute coronary syndrome, aortic dissection, myocardial infarction, unstable angina pectoris, cerebrovascular accident, or other Grade 3 or higher cardiovascular or cerebrovascular event within 6 months prior to the first dose
14. Major gastrointestinal surgery, or malabsorption syndrome, or are unable to swallow tablets that may impair the absorption of SC0245 tablets, or other active diseases or pathological conditions that may impact absorption, distribution, metabolism, excretion of SC0245 (such as uncontrollable nausea, vomiting, diarrhea, intestinal obstruction) as judged by the Investigator within 4 weeks before first dose of study drug.
15. Tertiary-interstitial effusion (e.g., pericardial, pleural, and peritoneal effusion) requiring repeated drainage or other treatments, but still could not be controlled within two weeks before first dose of study drug and are judged unsuitable to participate in the study by the Investigator.
16. Patients with other known malignant diseases. Exceptions: History of curative treatment for malignancy with no recurrence within 5 years; adequately treated non-melanoma skin cancer or lentigo malign; carcinoma in situ adequately treated with no signs of recurrence
17. UGT1A1 mutation.
18. Patients with underlying medical conditions (including laboratory abnormalities), alcohol or drug abuse or dependence that may affect study drug administration or the interpretation of drug toxicity or adverse events (AEs), or result in poor compliance, and are judged unsuitable to participate in the study by the Investigator.

Where this trial is running

Shanghai, Shanghai

• Shanghai Chest Hospital — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Study coordinator: SHUN LU, Prof

Conditions Small Cell Lung Cancer