Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Carboplatin

Osimertinib

Pemetrexed

Cisplatin

Mitogens

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

In Phase 1, Phase 2a and the investigational arm of Phase 2b, patients will receive their assigned dose of quaratusugene ozeplasmid (intravenous administration once every 21 days) plus osimertinib (80 mg fixed dose oral tablet taken daily starting on Day 1 through Day 21 of every 21-day treatment cycle) until disease progression or unacceptable toxicity.

In the control arm of Phase 2b, patients will receive platinum-based chemotherapy until disease progression or unacceptable toxicity.

Quaratusugene ozeplasmid is an experimental non-viral 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.

quaratusugene ozeplasmid

Osimertinib is a 3rd generation EGFR tyrosine kinase inhibitor (TKI) oral tablet administered daily, as indicated for treatment of patients with metastatic NSCLC whose tumors have EGFR genetic deletions or mutations.

osimertinib

Cisplatin and carboplatin are intravenously administered platinum agents that are combined with other cytotoxic chemotherapy agents such as pemetrexed.

Platinum-Based Chemotherapy

Sr Director, Clinical Operations

Chief Medical Officer

Kristi Okino

David Berz, MD

Katherine Schleich

Joni Richman

Robert M. Jotte, MD

Hannah Parks

Kendrith Rowland, MD

Missy Almand

Jake Brooks

John M. Wallmark, MD

John Waldron

Krishna K. Pachipala, MD

Carrie Friedman, RN, BSN, OCN

Alexander I. Spira, MD

Mark S. Berger, MD

The purpose of this randomized study is to determine the safety and efficacy of quaratusugene ozeplasmid (Reqorsa) added to osimertinib in NSCLC patients with activating EGFR mutations who have progressed while on treatment with osimertinib. Quaratusugene ozeplasmid consists of non-viral lipid nanoparticles that encapsulate a DNA plasmid with the TUSC2 tumor suppressor gene and is the first systemic gene therapy for cancer.

The study will comprise of a Phase 1 dose escalation and Phase 2 evaluations of safety and efficacy. In the Phase 1 dose escalation, patients will be enrolled in sequential cohorts treated with successively higher doses of quaratusugene ozeplasmid in combination with osimertinib. When the recommended Phase 2 dose (RP2D) is determined in Phase 1, Phase 2a will be initiated and patients will be enrolled in 2 parallel, non-randomized cohorts treated with quaratusugene ozeplasmid at the RP2D in combination with osimertinib. In Phase 2b, patients will be randomized to receive either quaratusugene ozeplasmid plus osimertinib or platinum-based chemotherapy.

Acclaim-1 is an open-label, multi-center, Phase 1/2 study evaluating quaratusugene ozeplasmid (Reqorsa) plus osimertinib (investigational arm) versus platinum-based chemotherapy (control arm) in patients with advanced metastatic or recurrent NSCLC.

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 (DLT) will be reviewed by a Safety Review Committee.

Phase 1 - Dose Escalation: The RP2D of quaratusugene ozeplasmid when given in combination with osimertinib will be identified.

Phase 2a: Once the RP2D of quaratusugene ozeplasmid is identified in Phase 1, 2 expansion cohorts will be enrolled to better characterize safety, tolerability, and preliminary anti-tumor activity of the combination therapy.

Phase 2b: Quaratusugene ozeplasmid in combination with osimertinib will be further evaluated using the RP2D identified in Phase 1. Patients may receive local therapy, such as radiation therapy, to progressing lesions prior to enrollment. Patients will be randomized to receive either the investigational arm or the control arm in a 1 to 1 ratio and stratified based on prior local radiotherapy.

Phase 1: 3+3 dose escalation to identify RP2D.

Phase 2: RP2D further evaluated in Phase 2a followed by parallel randomization in a 1:1 ratio to either investigational arm or control arm.

Quaratusugene Ozeplasmid (Reqorsa) and Osimertinib in Patients With Advanced Lung Cancer Who Progressed on Osimertinib

A Phase 1/2 Open-Label, Dose-Escalation and Clinical Response Study of Quaratusugene Ozeplasmid in Combination With Osimertinib in Patients With Advanced, Metastatic EGFR-Mutant, Metastatic Non-Small Cell Lung Cancer

RP2D, which will be the maximum tolerated dose (MTD) or, if the MTD is not defined by the safety data, RP2D will be determined based on an integrated assessment of all available clinical safety and preliminary efficacy data.

ORR (complete response \[CR\]+ partial response \[PR\]) according to RECIST using best overall response from baseline to disease progression or death.

PFS from randomization to disease progression or death. PFS according to RECIST.

PFS from first dose to disease progression or death. PFS according to RECIST.

ORR (CR+ PR) according to RECIST using best overall response from baseline to disease progression or death.

Concentration of quaratusugene ozeplasmid in whole blood samples.

TTP from first dose to disease progression. TTP according to RECIST.

OS from first dose until death or discontinuation due to withdrawal of consent.

DOR (CR + PR) according to RECIST from response to disease progression.

OS from randomization to death or discontinuation due to withdrawal of consent.

Treatment-related adverse events (AEs) graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events.

Genprex, Inc.

Antibodies

Pembrolizumab

Docetaxel

Immunoglobulins

Endothelial Growth Factors

Ramucirumab

Antibodies, Blocking

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

In Phase 1, the dose expansion portion of Phase 2 and the investigational arm of the randomized portion of Phase 2, patients will receive their assigned dose of quaratusugene ozeplasmid (via intravenous infusion) in combination with a fixed 200 mg dose of pembrolizumab (via intravenous infusion) once in every 21-day treatment cycle until disease progression or unacceptable toxicity.

In the control arm of the randomized portion of Phase 2, patients will receive either 75 mg/m2 docetaxel (via intravenous infusion) with or without 10 mg/kg ramucirumab (via intravenous infusion) -OR- investigator's choice of treatment. The treatment regimen for patients randomized to the control arm, must begin at Cycle 1 Day 1 and continue every 21 days until disease progression or unacceptable toxicity.

Quaratusugene ozeplasmid is an experimental non-viral therapy utilizing the TUSC2 gene, designed to target cancer cells by interrupting cell signaling pathways that allow cancer cells to grow, re-establishing pathways that promote cancer cell death and modulating the immune system response against cancer cells.

Pembrolizumab is a programmed death receptor-1 (PD-1) blocking antibody indicated for treatment of patients with metastatic NSCLC.

pembrolizumab

Docetaxel is a microtubule inhibitor indicated for locally advanced or metastatic NSCLC after platinum-based chemotherapy failure.

docetaxel

Ramucirumab is a human vascular endothelial growth factor receptor 2 (VEGFR2) antagonist indicated in combination with docetaxel for treatment of NSCLC with disease progression after platinum-based chemotherapy.

ramucirumab

Treatment will be administered during 21-day treatment cycles. The investigator's treatment must not include investigational drugs or therapies.

Investigator's Treatment of Choice

Alberto A Chiappori, MD

Brittany Gorr

Carly Lang

Jill Collins

Thomas Atkinson, MD

Daniel Morgensztern, MD

Minal Barve, MD

The purpose of this study is to determine the safety and efficacy of quaratusugene ozeplasmid (Reqorsa), in combination with pembrolizumab in patients with previously treated NSCLC. Quaratusugene ozeplasmid consists of non-viral lipid nanoparticles that encapsulate a DNA plasmid with the TUSC2 tumor suppressor gene, and is a systemic gene therapy.

The study will be conducted in 2 phases, a dose escalation phase (Phase 1) and a safety and efficacy evaluation phase (Phase 2). In Phase 1, patients will be enrolled in sequential cohorts treated with successively higher doses of quaratusugene ozeplasmid in combination with pembrolizumab to determine the recommended Phase 2 dose (RP2D). Phase 2 will be comprised of a dose expansion portion and a randomized portion. In the dose expansion portion, patients will be enrolled and treated with quaratusugene ozeplasmid at the RP2D in combination with pembrolizumab. In the randomized portion, patients will be randomized to receive either the investigational treatment of quaratusugene ozeplasmid at the RP2D in combination with pembrolizumab or a control treatment of either docetaxel +/- ramucirumab or the investigator's treatment of choice.

Acclaim-2 is a Phase 1/2 multicenter, open-label study of quaratusugene ozeplasmid in combination with pembrolizumab in patients with locally advanced or metastatic NSCLC with any PD-L1 TPS and NOT considered refractory to pembrolizumab, as defined by having achieved at least a 3-month clinical benefit to previous pembrolizumab-containing treatment.

The total duration of study for each patient will be dependent upon the safety, tolerability, and efficacy of the study treatment.

The Phase 1 portion of the study will involve a 3+3 dose escalation schema of quaratusugene ozeplasmid up to 0.12 mg/kg in combination with a fixed dose of pembrolizumab (200 mg) administered once via intravenous (IV) infusion during each 21-day treatment cycle. Three quaratusugene ozeplasmid doses will be tested (0.06, 0.09 and 0.12 mg/kg administered on Day 1 of a 21-day treatment cycle).

Phase 2 will involve a dose expansion portion and a randomized portion. In the dose expansion portion 36 patients will be enrolled to better characterize the safety and preliminary efficacy of quaratusugene in combination with pembrolizumab. Patients in the dose expansion portion will receive quaratusugene ozeplasmid at the RP2D determined in Phase 1 in combination with pembrolizumab once in every 21-day treatment cycle. When the PFS rate at 18 weeks has been evaluated for all patients in the dose expansion portion and been shown to meet the criteria for advancement to the randomized portion of Phase 2, the randomized portion of Phase 2 will be initiated. In the randomized portion of Phase 2, 126 patients will be randomized 2:1 to the investigational (quaratusugene ozeplasmid in combination with pembrolizumab) versus control (docetaxel with or without ramucirumab, or investigator's choice of treatment) treatment arms, respectively. Patients will be stratified by NSCLC histology (squamous versus nonsquamous predominant histology) for efficacy analysis purposes. The 84 patients randomized to the investigational arm will receive quaratusugene ozeplasmid, at the RP2D determined in Phase 1, administered in combination with 200 mg pembrolizumab once in every 21-day treatment cycle. The 42 patients randomized to the control arm may either receive docetaxel with or without ramucirumab, or a non-investigational treatment chosen by the investigator.

Phase 1: 3+3 dose escalation to identify RP2D.

Phase 2: RP2D expansion cohort followed by parallel randomization in a 2:1 ratio to either investigational arm or control arm.

Quaratusugene Ozeplasmid (Reqorsa) in Combination With Pembrolizumab in Previously Treated Non-Small Lung Cancer

A Phase 1/2 Open-Label, Dose-Escalation and Clinical Response Study of Quaratusugene Ozeplasmid in Combination With Pembrolizumab Versus Docetaxel With or Without Ramucirumab in Patients With Previously Treated Non-Small Cell Lung Cancer

RP2D which will be the MTD or if the MTD is not defined by the safety data, the RP2D will be determined based on an integrated assessment of all available clinical safety, PK, and preliminary efficacy data.

PFS rate at 18 weeks after first dose of study treatment. PFS according to RECIST.

PFS from first study treatment to disease progression or death. PFS according to RECIST.

OS from first study treatment to death or discontinuation due to withdrawal of consent.

Concentrations of quaratusugene ozeplasmid in whole blood samples.

Number of treatment-related AEs graded according to the NCI-CTCAE.

ORR (Complete Response \[CR\] + Partial Response \[PR\]) using best overall response from first study treatment to disease progression or death per RECIST compared to baseline tumor measurements.

ORR (CR + PR) using best overall response from randomization to disease progression or death per RECIST compared to baseline tumor measurements.

DCR (CR + PR + Stable Disease \[SD\]) using best overall response from randomization to death or discontinuation due to withdrawal of consent per RECIST compared to baseline tumor measurements.

Rare Diseases

Small Cell Lung Carcinoma

Small Cell Lung Cancer

Atezolizumab

Antibodies, Monoclonal

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.

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

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.

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.

atezolizumab

Jennifer Hege

Robert M Jotte, MD

Medical Oncology Clinical Call Center

Douglas Hart

David M Waterhouse, MD

Jeanne Schaffer

Bo Wang, MD

Jennifer Thompson

Anthony Van Ho, MD

Brenda Fisher, RN

Rachel Sanborn, MD

Christine Terraciano

Kartik Konduri, MD

Shelly Maxfield

Donald A Richards, MD

Carrie Friedman

Alexander I Spira, MD

Mark S Berger, MD

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).

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.

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.

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

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

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).

PFSR at 18 weeks according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).

PFS per RECIST 1.1. PFS is defined as time from Day 1 of maintenance therapy to disease progression or death.

Number of months from Day 1 of maintenance therapy to the date of death.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Quaratusugene Ozeplasmid (Reqorsa) and Osimertinib in Patients With Advanced Lung Cancer Who Progressed on Osimertinib	NCT04486833	Carcinoma, Non-...	quaratusugene o... osimertinib Platinum-Based ...	18 Years -	Genprex, Inc.
Quaratusugene Ozeplasmid (Reqorsa) in Combination With Pembrolizumab in Previously Treated Non-Small Lung Cancer	NCT05062980	Non Small Cell ...	quaratusugene o... pembrolizumab docetaxel ramucirumab Investigator's ...	18 Years -	Genprex, Inc.
Quaratusugene Ozeplasmid (Reqorsa) in Combination With Pembrolizumab in Previously Treated Non-Small Lung Cancer	NCT05062980	Non Small Cell ...	quaratusugene o... pembrolizumab docetaxel ramucirumab Investigator's ...	18 Years -	Genprex, Inc.
Quaratusugene Ozeplasmid (Reqorsa) and Atezolizumab Maintenance Therapy in ES-SCLC Patients	NCT05703971	Small Cell Lung...	quaratusugene o... atezolizumab	18 Years -	Genprex, Inc.
Quaratusugene Ozeplasmid (Reqorsa) and Osimertinib in Patients With Advanced Lung Cancer Who Progressed on Osimertinib	NCT04486833	Carcinoma, Non-...	quaratusugene o... osimertinib Platinum-Based ...	18 Years -	Genprex, Inc.

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