Quaratusugene Ozeplasmid (Reqorsa) and Atezolizumab Maintenance Therapy in ES-SCLC Patients
- Conditions
- Small Cell Lung Cancer Extensive Stage
- Interventions
- Biological: quaratusugene ozeplasmidBiological: atezolizumab
- Registration Number
- NCT05703971
- Lead Sponsor
- Genprex, Inc.
- Brief Summary
This clinical trial will evaluate the combination of quaratusugene ozeplasmid with atezolizumab as maintenance therapy for patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC).
The study is comprised of 2 phases, a dose selection phase (Phase 1) and a safety and efficacy evaluation phase (Phase 2).
- Detailed Description
Acclaim-3 is an open-label, multi-center, Phase 1/2 study evaluating the combination of quaratusugene ozeplasmid with atezolizumab as maintenance therapy for patients with ES-SCLC who did not develop tumor progression after receiving at least 3 cycles, and no more than 4 cycles, of induction therapy with carboplatin plus etoposide and atezolizumab.
Toxicities will be assessed by the Investigator using United States National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Serious Adverse Events and Dose Limiting Toxicities (DLTs) will be reviewed by a safety review committee.
Phase 1: Enrollment in Phase 1 is complete and the recommended Phase 2 dose (RP2D) of quaratusugene ozeplasmid when given in combination with atezolizumab was determined.
Phase 2: Enrollment has been initiated and enrolled patients are treated with quaratusugene ozeplasmid at the RP2D in combination with atezolizumab.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 62
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Male or female aged ≥18 years.
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Documented history of histologically or cytologically confirmed ES-SCLC, prior to starting treatment with the combination of atezolizumab, carboplatin, and etoposide
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Complete Response (CR), Partial Response (PR), or Stable Disease (SD) after receiving at least three cycles, and no more than four cycles, of atezolizumab, carboplatin, and etoposide.
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Eastern Cooperative Oncology Group performance status (ECOG PS) score from 0 to 1.
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Must be ≥28 days beyond major surgical procedures such as thoracotomy, laparotomy, or joint replacement, and must not have evidence of wound dehiscence, active wound infection, or comparable major residual complications of the surgery per Investigator assessment.
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Asymptomatic brain metastases must meet ALL criteria of the following (a-d):
- No history of seizures in the preceding six months.
- Definitive treatment must be completed ≥21 days prior to enrollment.
- Must be off steroids administered because of brain metastases or related symptoms for ≥7 days.
- If had previous brain irradiation, post-treatment imaging must demonstrate stability or regression of the brain metastases.
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Absolute neutrophil count (ANC) >1500/mm3, platelet count >100,000/mm3 within ≤28 days.
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Adequate renal function documented by serum creatinine of ≤1.5 mg/dL or calculated creatinine clearance >50 ml/min within ≤28 days.
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Adequate hepatic function as documented by serum bilirubin <1.5 mg/dL and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 X upper limit of normal (ULN) within ≤28 days.
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Stable cardiac condition with a left ventricular ejection fraction ≥40% within ≤28 days.
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If female of childbearing potential (FOCBP), must have negative serum pregnancy test (serum beta-human chorionic gonadotropin [β-hCG]) within ≤7 days of first dose.
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FOCBP and non-sterile men who are sexually active with FOCBP must agree to use two forms of contraception including one highly effective and one effective methods beginning ≥2 weeks prior to enrollment through for four months following the last dose of study treatment.
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If male, must agree to no sperm donation during study treatment and for an additional four months following the last dose of study treatment.
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Must have voluntarily signed an informed consent in accordance with institutional policies.
- Unable to tolerate atezolizumab treatment, leading to early treatment discontinuation or prolonged/frequent dosage modifications in previous atezolizumab treatment as determined by the Investigator.
- Received prior gene therapy.
- Received prophylactic cranial irradiation or consolidation thoracic radiation.
- Active systemic viral, bacterial, or fungal infection(s) requiring treatment.
- Serious concurrent illness or psychological, familial, sociological, geographical, or other concomitant conditions that, in the opinion of the Investigator, would not permit adequate follow-up and compliance with the study protocol.
- History of autoimmune disease requiring immunosuppression.
- History of myocardial infarction or unstable angina within ≤6 months.
- Known human immunodeficiency virus (HIV) infection or has active hepatitis infection.
- Female who is pregnant or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 2 atezolizumab Patients will be treated with the RP2D of quaratusugene ozeplasmid (IV administration once every 21 days) plus atezolizumab (1200 mg IV administration once every 21 days) until disease progression or unacceptable toxicity Phase 1 atezolizumab Up to 2 sequential dose selection cohorts will be treated with quaratusugene ozeplasmid (intravenous (IV) administration once every 21 days) plus atezolizumab (1200 mg IV administration once every 21 days) until disease progression or unacceptable toxicity. Quaratusugene ozeplasmid doses will be evaluated (0.09 \[starting dose\], and 0.12 mg/kg) until the RP2D is identified. Phase 2 quaratusugene ozeplasmid Patients will be treated with the RP2D of quaratusugene ozeplasmid (IV administration once every 21 days) plus atezolizumab (1200 mg IV administration once every 21 days) until disease progression or unacceptable toxicity Phase 1 quaratusugene ozeplasmid Up to 2 sequential dose selection cohorts will be treated with quaratusugene ozeplasmid (intravenous (IV) administration once every 21 days) plus atezolizumab (1200 mg IV administration once every 21 days) until disease progression or unacceptable toxicity. Quaratusugene ozeplasmid doses will be evaluated (0.09 \[starting dose\], and 0.12 mg/kg) until the RP2D is identified. Phase 1 atezolizumab Up to 2 sequential dose selection cohorts will be treated with quaratusugene ozeplasmid (intravenous (IV) administration once every 21 days) plus atezolizumab (1200 mg IV administration once every 21 days) until disease progression or unacceptable toxicity. Quaratusugene ozeplasmid doses will be evaluated (0.09 \[starting dose\], and 0.12 mg/kg) until the RP2D is identified. Phase 2 quaratusugene ozeplasmid Patients will be treated with the RP2D of quaratusugene ozeplasmid (IV administration once every 21 days) plus atezolizumab (1200 mg IV administration once every 21 days) or atezolizumab and hyaluronidase-tqjs (15 mL subcutaneous \[SQ\] administration once every 21 days) until disease progression or unacceptable toxicity Phase 2 atezolizumab Patients will be treated with the RP2D of quaratusugene ozeplasmid (IV administration once every 21 days) plus atezolizumab (1200 mg IV administration once every 21 days) or atezolizumab and hyaluronidase-tqjs (15 mL subcutaneous \[SQ\] administration once every 21 days) until disease progression or unacceptable toxicity Phase 1 quaratusugene ozeplasmid Up to 2 sequential dose selection cohorts will be treated with quaratusugene ozeplasmid (intravenous (IV) administration once every 21 days) plus atezolizumab (1200 mg IV administration once every 21 days) until disease progression or unacceptable toxicity. Quaratusugene ozeplasmid doses will be evaluated (0.09 \[starting dose\], and 0.12 mg/kg) until the RP2D is identified.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) - Phase 1 First 21-days at each dose level The MTD and/or RP2D of the combination of quaratusugene ozeplasmid and atezolizumab.
Note: if a MTD is not determined, the RP2D will be selected based on all available data (safety, PK, PD, and preliminary efficacy).Progression-Free Survival Rate (PFSR) - Phase 2 18-weeks from Day 1 of maintenance therapy PFSR at 18 weeks according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).
- Secondary Outcome Measures
Name Time Method Safety Profile - Phase 1 Approximately 6 months Adverse events according to CTCAE v5.0
Progression-free Survival (PFS) - Phase 1 & Phase 2 Approximately 5 months PFS per RECIST 1.1. PFS is defined as time from Day 1 of maintenance therapy to disease progression or death.
Overall Survival (OS) - Phase 1 & Phase 2 Approximately 18 months Number of months from Day 1 of maintenance therapy to the date of death.
Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 1 & Phase 2 First 21-day treatment cycle Concentration of quaratusugene ozeplasmid in whole blood samples.
Trial Locations
- Locations (9)
Rocky Mountain Cancer Centers, LLP
🇺🇸Lone Tree, Colorado, United States
Washington University School of Medicine - Siteman Cancer Center
🇺🇸Saint Louis, Missouri, United States
Northwest Cancer Specialists, P.C.
🇺🇸Vancouver, Washington, United States
Willamette Valley Cancer Institute (Oregon)
🇺🇸Eugene, Oregon, United States
Oncology_Hematology Care Clinical Trials, LLC
🇺🇸Fairfield, Ohio, United States
Texas Oncology - Northeast Texas
🇺🇸Tyler, Texas, United States
Providence Cancer Institute
🇺🇸Portland, Oregon, United States
Texas Oncology - DFW
🇺🇸Dallas, Texas, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States