Clinical trial NCT05703971: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Small Cell Lung Cancer Extensive Stage
Keywords: atezolizumab
atezolizumab and hyaluronidase-tqjs
Tumor Suppressor Gene 2 (TUSC2)
Lipid Nanoparticle (LNP)
Gene Therapy
TECENTRIQ
ES-SCLC
REQORSA
quaratusugene ozeplasmid
Lead sponsor: Genprex, Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-30
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1: 3+3 dose selection to identify RP2D. Phase 2: open label, non-randomized treatment with quaratusugene ozeplasmid at RP2D in combination with atezolizumab.
Primary purpose: TREATMENT

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.

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):

  1. No history of seizures in the preceding six months.
  2. Definitive treatment must be completed ≥21 days prior to enrollment.
  3. Must be off steroids administered because of brain metastases or related symptoms for ≥7 days.
  4. 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

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) - Phase 1
timeFrame: First 21-days at each dose level
measure: Progression-Free Survival Rate (PFSR) - Phase 2
timeFrame: 18-weeks from Day 1 of maintenance therapy
Secondary outcomes:
measure: Safety Profile - Phase 1
timeFrame: Approximately 6 months
measure: Progression-free Survival (PFS) - Phase 1 & Phase 2
timeFrame: Approximately 5 months
measure: Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 1 & Phase 2
timeFrame: First 21-day treatment cycle
measure: Overall Survival (OS) - Phase 1 & Phase 2
timeFrame: Approximately 18 months
Other outcomes:
Locations:
city: Lone Tree
country: United States
facility: Rocky Mountain Cancer Centers, LLP
state: Colorado
city: Saint Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: Cincinnati
country: United States
facility: Oncology_Hematology Care Clinical Trials, LLC
state: Ohio
city: Cincinnati
country: United States
facility: Oncology_Hematology Care Clinical Trials, LLC
state: Ohio
city: Cincinnati
country: United States
facility: Oncology_Hematology Care Clinical Trials, LLC
state: Ohio
city: Cincinnati
country: United States
facility: Oncology_Hematology Care Clinical Trials, LLC
state: Ohio
city: Fairfield
country: United States
facility: Oncology_Hematology Care Clinical Trials, LLC
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute (Oregon)
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Institute
state: Oregon
city: Portland
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Tigard
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Dallas
country: United States
facility: Texas Oncology - DFW
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Washington
Study officials:
affiliation: Genprex, Inc.
name: Mark S Berger, MD
role: STUDY_DIRECTOR
References: