Quaratusugene Ozeplasmid (Reqorsa) and Atezolizumab Maintenance Therapy in ES-SCLC Patients (Acclaim-3)

Genprex

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Small Cell Lung Cancer Extensive Stage

Treatments: Biological: quaratusugene ozeplasmid; Biological: atezolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05703971

ONC-005

Details and patient eligibility

About

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).

Full 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.

Enrollment: 62 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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62 participants in 2 patient groups

Phase 1

Experimental group

Description:

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.

Treatment:

Biological: atezolizumab

Biological: quaratusugene ozeplasmid

Phase 2

Experimental group

Description:

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

Treatment:

Biological: atezolizumab

Biological: quaratusugene ozeplasmid