SNB-101 for Treatment of Extensive Stage Small Cell Lung Cancer

Официальное название

A Phase 1b/2, Open-Label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of SNB-101, in Extensive Stage Small Cell Lung Cancer.

Обзор

The purpose of the Phase 1 research is to test the safety, tolerability, maximum tolerated dose, and pharmacokinetics (PK- the study of how a medicine moves through subject body. It looks at how the drug is absorbed, travels in your blood, reaches different parts of subject body, and is eventually broken down and removed) of the SNB-101.The Phase 2 is to determine the optimal dose (amount of medicine that works best to treat a condition while causing the fewest side effects) of SNB-101 for further research and to collect a further information on PK, safety and tolerability. Once subject has completed assessments during screening and if subject is found eligible to participate in the study, study drug will be given by intravenous infusion on day 1 and day 15 of each cycle treatment. Throughout the treatment period, the study doctor will monitor subject for any changes to subject health. While subject is taking the study drug, we will ask subject the following: * How subject are feeling. * If subject has experienced any side effects. * If subject is taking other medications or if there are changes to the medications subject was taking before. The study drug will be taken over multiple cycles. A cycle is the time between the start of 1 round of treatment until the start of the next round. In this study, each treatment cycle is of 28 days.

Вмешательства

• Препарат SNB-101
  SNB-101 is a nanoparticle formulation of SN-38 administered intravenously. Subject enrolled for each dose level cohort of 50/80 mg/m2, 60/96 mg/m² and 70/112 mg/m2 will be administered intravenously over 90 minutes at Day 1 and Day 15 of each cycle

Первичные конечные точки

• Dose Limiting Toxicity (DLT) according to CTCAE version 5.0 in Phase 1 [Срок оценки: Dose limiting toxicities will be evaluated during the first treatment cycle (28 days)]
• Treatment discontinuation/dose reduction due to Adverse Events (AEs) in Phase 1 [Срок оценки: Day 1 through study completion, an average of 2 years]
• Number of Adverse Events (AE) that occurs in Phase 1Number of Adverse Events (AE) that occurs in Phase 1 [Срок оценки: Adverse events will be recorded from informed consent through 28 days (±7 days) after the last dose of study drug]
• Laboratory Parameters in Phase 1 [Срок оценки: For hematology, clinical chemistry and coagulation: at Screening; at Days 1, 8, 15, and 22 of Cycle 1; at Days 1 and 15 of each subsequent treatment cycle (each cycle is 28 days); and at End of Treatment (EOT) For urinanalysis: at screening, day 1 of cy]
• Vital Signs in Phase 1 [Срок оценки: Baseline through study completion, an average of 2 years]
• ECG Parameters in Phase 1 [Срок оценки: On Day 1 of cycle 1, cycle 2, cycle 3 and cycle 4. (Each cycle is 28 days)]
• Chest X-ray (CXR) Abnormalities in Phase 1 [Срок оценки: Baseline (Screening) through study completion, an average of 2 years]
• Optimized Dose of SNB-101 in Phase 2 [Срок оценки: Day 1 through study completion, an average of 2 years]

Вторичные конечные точки (12)

• Objective Response Rate (ORR) in Phase 1 and 2 [Срок оценки: At every 2 cycles (each cycle is 28 days) from baseline (Cycle 1 Day 1) until disease progression or initiation of subsequent chemotherapy (up to 2 years).]
• Duration of Response (DOR) in Phase 1 and 2Duration of Response (DOR) in Phase 1 and 2 [Срок оценки: At every 2 cycles (each cycle is 28 days) from baseline (cycle 1 day 1) until disease progression or initiation of subsequent chemotherapy (up to 2 years).]
• Progression-Free Survival (PFS) in Phase 1 and 2 [Срок оценки: At every 2 cycles (each cycle is 28 days) from baseline (Cycle 1 Day 1) until disease progression or initiation of subsequent chemotherapy (up to 2 years).]
• Overall Survival (OS) in Phase 1 and 2 [Срок оценки: Upto 2 years]
• Disease Control Rate (DCR) Phase 1 [Срок оценки: At every 2 cycles (each cycle is 28 days) from baseline (Cycle 1 Day 1) until disease progression or initiation of subsequent chemotherapy (up to 2 years).]
• Overall Survival Rate at 12 Months in Phase 2 [Срок оценки: 12 months]
• Maximum plasma concentration [Cmax] in Phase 1 and 2 [Срок оценки: Up to 168 hours post-dose on Cycle 1 Day 1 and Cycle 3 Day 1 (each cycle is 28 days); and up to 24 hours post-dose on Cycle 2 Day 1 and Cycle 4 Day 1 (sparse sampling; each cycle is 28 days).]
• Time to maximum plasma concentration [tmax] in Phase 1 and 2 [Срок оценки: Up to 168 hours post-dose on Cycle 1 Day 1 and Cycle 3 Day 1 (each cycle is 28 days); and up to 24 hours post-dose on Cycle 2 Day 1 and Cycle 4 Day 1 (sparse sampling; each cycle is 28 days).]
• Last Measurable Plasma Concentration (Clast) in Phase 1 and 2 [Срок оценки: Up to 168 hours post-dose on Cycle 1 Day 1 and Cycle 3 Day 1 (each cycle is 28 days); and up to 24 hours post-dose on Cycle 2 Day 1 and Cycle 4 Day 1 (sparse sampling; each cycle is 28 days).]
• Time of Last Measurable Concentration (Tlast) in Phase 1 and 2 [Срок оценки: Up to 168 hours post-dose on Cycle 1 Day 1 and Cycle 3 Day 1 (each cycle is 28 days); and up to 24 hours post-dose on Cycle 2 Day 1 and Cycle 4 Day 1 (sparse sampling; each cycle is 28 days).]
• Area under the concentration-time curve from zero to a definite time [AUC(0-t)] in Phase 1 and 2 [Срок оценки: Up to 168 hours post-dose on Cycle 1 Day 1 and Cycle 3 Day 1 (each cycle is 28 days); and up to 24 hours post-dose on Cycle 2 Day 1 and Cycle 4 Day 1 (sparse sampling; each cycle is 28 days).]
• Area under the concentration-time curve from zero to an infinite time [AUC(0-inf)] in Phase 1 and 2 [Срок оценки: Up to 168 hours post-dose on Cycle 1 Day 1 and Cycle 3 Day 1 (each cycle is 28 days); and up to 24 hours post-dose on Cycle 2 Day 1 and Cycle 4 Day 1 (sparse sampling; each cycle is 28 days).]

Критерии участия

Критерии включения

• Male or female patients over 18 years of age.
• Male or fertile female patients who have agreed to comply with effective contraceptive methods as required by this protocol and the specified contraceptive period.
• Participants must have a cytologically or histologically confirmed small cell lung cancer which is locally advanced or metastatic and has progressed on or after standard therapy for advanced disease containing platinum-based therapy plus etoposide with or without atezolizumab or durvalumab immunotherapy and is not suitable for complete surgical resection.
• Have measurable or evaluable disease consistent with RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1
• With life expectancy more than 12 weeks
• Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Have adequate hematological, renal, and liver function as defined by the following (lab test can be repeated during screening):
• Have recovered to grade 1 or better to (CTCAE version 5.0) from any reversible side effects of previous treatments. Note: Grade 2 alopecia and Grade 2 sensory neuropathy are not exclusionary.
• No major surgery, no antineoplastic or experimental therapy, and no direct radiation therapy to a hematopoietic site within 4 weeks prior to baseline, and no biologic drugs, nitrosoureas or mitomycin C administered within 6 weeks prior to baseline.
• Fully informed regarding the investigational nature of the study protocol and is capable of signing an Institutional Review Board/Ethics Committee-approved informed consent form.

Критерии исключения

• Patients in whom the homozygous variant alleles UGT1A1\*28 or UGT1A1\*6 are confirmed through UGT1A1 genotype testing at screening (or through previously conducted testing), or patients with heterozygous variant alleles UGT1A1\*6/\*28. (For Phase 1 only)
• Female patients who are pregnant, lactating (breast feeding) or planning a pregnancy during the course of study.
• Known or suspected intolerance or hypersensitivity to the main ingredient or any of the excipients of SNB-101.
• Patients deemed unsuitable or ineligible for participation in this clinical trial as judged by the Principal Investigator.

Medical History or Current Pathological Conditions and Diseases

• Known uncontrolled symptomatic heart failure.
• History of alcohol abuse or other substance abuse within 1 year prior to screening.
• Have intestinal palsy or bowel obstruction.
• Have chronic inflammatory bowel disease.
• Are on dialysis.
• Patients with any evidence of current ILD or pneumonitis or a prior history of interstitial lung disease (ILD) or non-infectious pneumonitis requiring high-dose glucocorticoids.
• Patients with clinically significant congestive heart failure that is uncontrolled.
• Have multiple ascites or pleural effusion.
• Have hematologic malignancy (including lymphoma).
• Have severe infections or other uncontrolled active infections that require the administration of antibiotics, antivirals, or other anti-infective agents that may affect safety or efficacy assessments during the clinical study, as determined by the investigator.
• When the QTc interval exceeds 480 msec\* (same standard for both men and women). \* Fridericia's QT correction formula
• Positive for Human Immunodeficiency Virus (HIV).
• Patients with known active hepatitis B (e.g., HBsAg response positive and HBV DNA detected) or hepatitis C (e.g., anti-HCV positive and HCV RNA \[qualitatively\]) detected).
• Central nervous system or brain metastases with clinically significant symptoms requiring systemic corticosteroids at least 2 weeks prior to baseline. (however, participants who have completed treatment and recovered from the acute phase of radiation therapy or surgery may participate in this study.).

Patients Who Have Received, are Receiving, or Cannot Discontinue the Following Medications or Therapies.

• Have received another investigational drug within the last 4 weeks prior to screening.
• If additional anticancer therapy\* other than the investigational drug is required during the clinical trial participation period. (However, localized radiation therapy for palliation purposes, such as for bone pain, bronchial obstruction, or skin lesions, is allowed).
• Surgery, radiation (chemotherapy), chemotherapy, targeted therapy (small molecule drugs, monoclonal antibodies), immunotherapy (biological agents), or hormone therapy, etc.
• If strong CYP3A4 inducer was administered within 2 weeks before baseline : (Phenytoin, carbamazepine, rifamycin (rifampicin, rifabutin, rifapentine), phenobarbital, etc., Preparations containing St. John's wort.
• Have received a strong CYP3A4 and/or UGT1A1 inhibitor (azole antifungal agents \[ketoconazole, fluconazole, itraconazole, miconazole, voriconazole, etc.\], macrolide antibiotics \[erythromycin, clarithromycin, etc.\], antiretroviral agents \[atazanavir, ritonavir, indinavir, lopinavir, nelfinavir, saquinavir, telaprevir\], sorafenib, diltiazem hydrochloride, nefazodone, gemfibrozil, nifedipine, etc., or grapefruit juice) within 1 week prior to baseline
• Will require administration of neuromuscular blockers, peripheral muscle relaxants, etc. during the study : Non-depolarizing neuromuscular blockers (such as succinylcholine) and depolarizing neuromuscular blockers (such as rocuronium)
• Will require lapatinib during the study.
• When administration of live herbal medicine detoxified vaccine is required during the clinical trial participation period: Yellow fever vaccine, etc.
• Are taking a drug during the study that in the judgment of the investigator will have a significant effect on liver metabolism or kidney excretion. However, taking such a drug is permitted if (a) it was taken more than 4 weeks prior to baseline.
• If the participant is deemed to be taking medications (including over-the-counter drugs, herbs, or homeopathic remedies) that significantly affect the action, metabolism, and excretion of the IP, as well as its efficacy and safety of the IP, as determined by the investigator. (However, if the participant has been taking the same dose of medication for at least 1 week prior to baseline \[excluding drugs taken daily; if taken regularly or periodically, it is included\], they are exempt).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Сербия · 1 центр

• The Institute for Pulmonary Diseases of Vojvodina — Kamenitz

Идентификаторы

NCT: NCT07391813 · SNB-101-101*

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗