Reqorsa + Osimertinib for Advanced Lung Cancer

(Acclaim-1 Trial)

Recruiting at 9 trial locations

Overseen By Sr Director, Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Genprex, Inc.

Must be taking: Osimertinib

Must not be taking: Gene therapy

Disqualifiers: Other genetic mutations, active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 63

158 Participants Needed

Trial Summary

What is the purpose of this trial?

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 is comprised of a Phase 1 dose escalation portion and two Phase 2 portions evaluating safety and efficacy. Enrollment in the Phase 1 dose escalation portion is complete and the recommended Phase 2 dose (RP2D) was determined. Phase 2a has initiated and enrolled patients are 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.

Will I have to stop taking my current medications?

The trial requires a minimum 10-day period without taking osimertinib before enrollment. It does not specify if you need to stop other medications, so it's best to discuss with the trial team.

What data supports the effectiveness of the drug Osimertinib for advanced lung cancer?

Osimertinib has shown effectiveness in treating advanced non-small cell lung cancer (NSCLC) with specific EGFR mutations, achieving significant tumor response rates in clinical trials. In particular, it was approved based on its ability to shrink tumors in patients with the EGFR T790M mutation, with response rates of 57% and 61% in two major studies. ^{1 2 3 4 5}

What safety data exists for the treatment Reqorsa + Osimertinib in humans?

Osimertinib, also known as Tagrisso, has been used in treating advanced lung cancer and is generally well tolerated. Common side effects include diarrhea, rash, dry skin, and nail issues, with some patients experiencing more severe effects like low blood cell counts and fatigue. No new safety concerns have been identified in recent studies. ^{1 2 4 5 6}

What makes the drug Reqorsa + Osimertinib unique for advanced lung cancer?

The combination of Reqorsa (Quaratusugene Ozeplasmid) and Osimertinib is unique because it targets specific genetic mutations in advanced lung cancer, potentially offering a more personalized treatment approach compared to standard therapies. This combination aims to enhance the effectiveness of Osimertinib, which is already used to treat certain types of lung cancer, by adding a novel gene therapy component. ^{7 8 9 10 11}

Research Team

Mark S. Berger, MD

Principal Investigator

Genprex, Inc.

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer (NSCLC) who have previously responded to osimertinib but now show disease progression. Participants must have adequate organ function, no recent major surgeries, controlled brain metastases if present, and agree to use two forms of contraception. Those with HIV, active hepatitis, or other mutations treatable by approved therapies are excluded.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer has grown despite taking osimertinib, and it can be measured by scans.

FOCBP and non-sterile male patients with female partner(s) of childbearing potential must agree to use 2 forms of contraception including 1 highly effective and 1 effective method beginning ≥2 weeks prior to enrollment through 4 months following the last dose of study treatment

Exclusion Criteria

My cancer has specific genetic mutations treatable with approved drugs.

I have undergone gene therapy before.

I haven't had a heart attack or unstable chest pain in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 - Dose Escalation

The RP2D of quaratusugene ozeplasmid when given in combination with osimertinib has been identified

First 21-day treatment cycle for each dose level cohort

Intravenous administration once every 21 days

Phase 2a

Expansion cohort to better characterize safety, tolerability, and preliminary anti-tumor activity of the combination therapy

Approximately 11 months

Intravenous administration once every 21 days

Phase 2b

Patients randomized to receive either quaratusugene ozeplasmid plus osimertinib or platinum-based chemotherapy

Approximately 11 months

Intravenous administration once every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 9 months

Treatment Details

Interventions

• Osimertinib
• Quaratusugene Ozeplasmid

Trial Overview The study tests quaratusugene ozeplasmid (Reqorsa), a gene therapy combined with osimertinib versus platinum-based chemotherapy in NSCLC patients after osimertinib failure. It includes dose escalation to find the safest effective dose followed by safety and efficacy evaluations comparing the new combination against standard chemotherapy.

Participant Groups

Group I: Investigational Experimental Treatment 2 Interventions

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.

Group II: Control Active Control 1 Intervention

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

Osimertinib is already approved in United States, European Union for the following indications:

Approved in United States as Tagrisso for:

• Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
• Metastatic EGFR T790M mutation-positive NSCLC

Approved in European Union as Tagrisso for:

• Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
• Metastatic EGFR T790M mutation-positive NSCLC

Who Is Running the Clinical Trial?

Genprex, Inc.

Lead Sponsor

Trials

4

Recruited

250+

Findings from Research

Osimertinib is an oral medication specifically designed to target the EGFR T790M mutation in advanced non-small cell lung cancer (NSCLC), which helps overcome resistance to previous EGFR TKI therapies.

It received accelerated approval in the USA in November 2015 for patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed after EGFR TKI treatment, and is currently undergoing further development for broader treatment applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. Greig, SL.[2022]

Osimertinib (TAGRISSO) received accelerated FDA approval for treating metastatic non-small cell lung cancer with the EGFR T790M mutation, showing significant tumor response rates of 57% and 61% in two major trials involving 411 patients.

While osimertinib demonstrated promising efficacy, common side effects included diarrhea (42%) and rash (41%), with 28% of patients experiencing severe adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Khozin, S., Weinstock, C., Blumenthal, GM., et al.[2022]

In a retrospective analysis of 32 patients with EGFR T790M-mutant non-small-cell lung cancer, osimertinib showed a 50% objective response rate and a median progression-free survival of 11.3 months, indicating its efficacy in clinical practice.

The median overall survival was 18.3 months, with better outcomes observed in patients without cerebral metastases and those with better performance status, highlighting the importance of these factors in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. Knetki-Wróblewska, M., Kowalski, DM., Czyżewicz, G., et al.[2022]

Osimertinib significantly improves disease-free survival (DFS) in adults with completely resected, early-stage EGFR mutation-positive non-small cell lung cancer (NSCLC), as shown in the pivotal ADAURA trial, regardless of prior adjuvant chemotherapy.

The treatment is well tolerated with a manageable safety profile, and it does not negatively impact health-related quality of life, making it a suitable option for adjuvant therapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. Frampton, JE.[2022]

Osimertinib (AZD9291) is effective in prolonging survival for non-small cell lung cancer patients with EGFR mutations, but resistance to the drug is a common issue, prompting the need to explore resistance mechanisms.

In this study, AZD9291-resistant NSCLC cell lines were established, revealing significant changes in circular RNA (circRNA) expression profiles, which may contribute to drug resistance and could serve as potential targets for future gene therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines. Chen, T., Luo, J., Gu, Y., et al.[2022]

Osimertinib (Tagrisso) is an approved adjuvant treatment for non-small cell lung cancer patients with specific tumor mutations, highlighting its targeted therapeutic approach.

Common side effects of osimertinib include blood-related issues like leukopenia and thrombocytopenia, as well as gastrointestinal and skin reactions, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Adjuvant Drug for Lung Cancer. Aschenbrenner, DS.[2023]

In a patient with metastatic castration-resistant prostate cancer (mCRPC), four cycles of radioligand therapy (RLT) using 177Lu-PSMA I&T resulted in over 97% destruction of metastatic tumors, indicating high efficacy of this treatment.

The study highlights the need for individualized dosimetry to account for variations in tumor response and suggests that measuring 177Lu-PSMA activity concentrations could improve routine dosimetry practices, while also noting that the first cycle of RLT has the most significant impact on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiomics Analysis for 177Lu-DOTAGA-(l-y)fk(Sub-KuE) Targeted Radioligand Therapy Dosimetry in Metastatic Prostate Cancer-A Model Based on Clinical Example. Kelk, E., Ruuge, P., Rohtla, K., et al.[2021]

In a study of 54 patients with advanced metastatic castration-resistant prostate cancer (mCRPC), 79% showed a significant decrease in PSA levels after three cycles of [177Lu]Lu-PSMA-617 radio-ligand therapy, indicating a strong therapeutic response.

The treatment was well-tolerated, with a median overall survival of 119 weeks and a median progression-free survival of 25 weeks, suggesting that PSMA-RLT can be an effective option for patients with mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome of standardized 177Lu-PSMA-617 therapy in metastatic prostate cancer patients receiving 7400 MBq every 4 weeks. Rasul, S., Hacker, M., Kretschmer-Chott, E., et al.[2021]

Zoledronic acid is the only FDA-approved bisphosphonate for preventing skeletal-related events (SREs) in patients with metastatic castrate resistant prostate cancer (mCRPC), while denosumab, a monoclonal antibody, effectively inhibits bone resorption by targeting RANK-L.

Alpharadin is the first radiopharmaceutical to demonstrate a significant overall survival benefit in mCRPC, highlighting advancements in treatment options that help manage complications from bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone-targeted therapies in metastatic castration-resistant prostate cancer: evolving paradigms. El-Amm, J., Freeman, A., Patel, N., et al.[2021]

Bone metastases in metastatic castration-resistant prostate cancer (mCRPC) significantly impact patient quality of life and are a leading cause of disability and death, highlighting the need for effective management strategies.

Current treatments like zoledronic acid, denosumab, and radium-223 have been shown to reduce skeletal-related events and improve survival, with radium-223 being the first bone-targeting agent to demonstrate improved survival and reduced pain in mCRPC patients without visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting bone metastases in prostate cancer: improving clinical outcome. Body, JJ., Casimiro, S., Costa, L.[2022]

In a phase 1/2 study involving 80 patients with metastatic, castration-resistant prostate cancer, the combination of sunitinib, docetaxel, and prednisone showed a confirmed prostate-specific antigen (PSA) response rate of 56.4%, indicating significant efficacy in this patient population.

The treatment was moderately well tolerated, with the most common severe side effects being neutropenia and fatigue, and it resulted in median progression-free and overall survival times of 12.6 and 21.7 months, respectively, suggesting a potential benefit for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sunitinib in combination with docetaxel and prednisone in chemotherapy-naive patients with metastatic, castration-resistant prostate cancer: a phase 1/2 clinical trial. Zurita, AJ., George, DJ., Shore, ND., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of osimertinib in patients with lung adenocarcinoma in clinical practice - the Expanded Drug Access Program in Poland. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Osimertinib: A Review in Completely Resected, Early-Stage, EGFR Mutation-Positive NSCLC. [2022]

5. Singapore pubmed.ncbi.nlm.nih.gov

Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

New Adjuvant Drug for Lung Cancer. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Radiomics Analysis for 177Lu-DOTAGA-(l-y)fk(Sub-KuE) Targeted Radioligand Therapy Dosimetry in Metastatic Prostate Cancer-A Model Based on Clinical Example. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Clinical outcome of standardized 177Lu-PSMA-617 therapy in metastatic prostate cancer patients receiving 7400 MBq every 4 weeks. [2021]

9. Egypt pubmed.ncbi.nlm.nih.gov

Bone-targeted therapies in metastatic castration-resistant prostate cancer: evolving paradigms. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Targeting bone metastases in prostate cancer: improving clinical outcome. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Sunitinib in combination with docetaxel and prednisone in chemotherapy-naive patients with metastatic, castration-resistant prostate cancer: a phase 1/2 clinical trial. [2023]