Quaratusugene Ozeplasmid (Reqorsa) and Atezolizumab Maintenance Therapy in ES-SCLC Patients

Official title

A Phase 1/2 Clinical Trial of Quaratusugene Ozeplasmid and Atezolizumab Maintenance Therapy in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC)

Overview

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.

Interventions

• Biological quaratusugene ozeplasmid
  Quaratusugene ozeplasmid is an experimental nonviral immunogene therapy utilizing the TUSC2 gene, designed to target cancer cells by interrupting cell signaling pathways that allow cancer cells to grow, reestablishing pathways that promote cancer cell death and modulating the immune response against cancer cells.
• Biological atezolizumab
  Atezolizumab is a monoclonal antibody that belongs to a class of drugs that binds to the programmed death-receptor 1 ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.

Primary outcome measures

• Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) - Phase 1 [Time frame: First 21-days at each dose level]
• Progression-Free Survival Rate (PFSR) - Phase 2 [Time frame: 18-weeks from Day 1 of maintenance therapy]

Secondary outcome measures (4)

• Safety Profile - Phase 1 [Time frame: Approximately 6 months]
• Progression-free Survival (PFS) - Phase 1 & Phase 2 [Time frame: Approximately 5 months]
• Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 1 & Phase 2 [Time frame: First 21-day treatment cycle]
• Overall Survival (OS) - Phase 1 & Phase 2 [Time frame: Approximately 18 months]

Eligibility criteria

Inclusion criteria

• Male or female aged ≥18 years.
• Documented history of histologically or cytologically confirmed ES-SCLC, prior to starting treatment with the combination of atezolizumab, carboplatin, and etoposide
• 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.
• Eastern Cooperative Oncology Group performance status (ECOG PS) score from 0 to 1.
• 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.
• 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.
• Absolute neutrophil count (ANC) >1500/mm3, platelet count >100,000/mm3 within ≤28 days.
• Adequate renal function documented by serum creatinine of ≤1.5 mg/dL or calculated creatinine clearance >50 ml/min within ≤28 days.
• 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.
• Stable cardiac condition with a left ventricular ejection fraction ≥40% within ≤28 days.
• 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.
• 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.
• If male, must agree to no sperm donation during study treatment and for an additional four months following the last dose of study treatment.
• Must have voluntarily signed an informed consent in accordance with institutional policies.

Exclusion criteria

• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 17 centers

• Rocky Mountain Cancer Centers, LLP — Lone Tree
• Washington University School of Medicine - Siteman Cancer Center — St Louis
• Gabrail Cancer Center Research — Canton
• Oncology_Hematology Care Clinical Trials, LLC — Cincinnati
• Oncology_Hematology Care Clinical Trials, LLC — Cincinnati
• Oncology_Hematology Care Clinical Trials, LLC — Cincinnati
• Oncology_Hematology Care Clinical Trials, LLC — Cincinnati
• Oncology_Hematology Care Clinical Trials, LLC — Fairfield
• … and 9 more centers

Identifiers

NCT: NCT05703971 · ONC-005

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗