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

Sponsor

Genprex, Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05703971

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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 will be conducted in 2 phases, a dose selection phase (Phase 1) and a safety and efficacy evaluation phase (Phase 2).

Condition or Disease	Intervention/Treatment	Phase
Small Cell Lung Cancer Extensive Stage	Biological: quaratusugene ozeplasmid Biological: atezolizumab	Phase 1/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: In Phase 1 dose selection, patients will be enrolled in sequential cohorts treated with successively higher doses of quaratusugene ozeplasmid in combination with atezolizumab. The recommended Phase 2 dose (RP2D) of quaratusugene ozeplasmid when given in combination with atezolizumab will be identified.

Phase 2: Quaratusugene ozeplasmid in combination with atezolizumab will be further evaluated using the RP2D identified in Phase 1.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

62 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Feb 1, 2026

Anticipated Study Completion Date :

Aug 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1 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.	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. Other Names: REQORSA 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. Other Names: TECENTRIQ
Experimental: Phase 2 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	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. Other Names: REQORSA 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. Other Names: TECENTRIQ

Arm

Intervention/Treatment

Experimental: Phase 1

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.

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.

Other Names:

REQORSA

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.

Other Names:

TECENTRIQ

Experimental: Phase 2

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

Biological: quaratusugene ozeplasmid

Other Names:

REQORSA

Biological: atezolizumab

Other Names:

TECENTRIQ

Outcome Measures

Primary Outcome Measures

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

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.
Pharmacokinetics (PK) of Quaratusugene Ozeplasmid - Phase 1 & Phase 2 [First 21-day treatment cycle]
Concentration of quaratusugene ozeplasmid in whole blood samples.
Overall Survival (OS) - Phase 1 & Phase 2 [Approximately 18 months]
Number of months from Day 1 of maintenance therapy to the date of death.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 3 cycles, and no more than 4 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 be ≥10 days beyond minor surgical procedures such as biopsy of subcutaneous tumors, pleuroscopy, etc., 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): a. No history of seizures in the preceding 6 months; b. Definitive treatment must be completed ≥21 days prior to enrollment; c. Must be off steroids administered because of brain metastases or related symptoms for ≥7 days; d. 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 ≤21 days.
Adequate renal function documented by serum creatinine of ≤1.5 mg/dL or calculated creatinine clearance >50 ml/min within ≤21 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 ≤21 days.
Stable cardiac condition with a left ventricular ejection fraction ≥40% within ≤21 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 men who are sexually active with FOCBP must agree to use 2 forms of contraception during the study period and for 4 months following the last dose of study treatment.
If male, must agree to no sperm donation during study treatment and for an additional 4 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.