Quaratusugene Ozeplasmid + Atezolizumab for Small Cell Lung Cancer

(Acclaim-3 Trial)

Recruiting at 12 trial locations

Overseen By Chief Medical Officer

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Genprex, Inc.

Must be taking: Atezolizumab

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: 42

62 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for individuals with extensive stage small cell lung cancer (ES-SCLC). Researchers aim to determine if a combination of quaratusugene ozeplasmid (Reqorsa) and atezolizumab (Tecentriq) can sustain positive outcomes after initial treatments. The study begins by identifying the optimal dose and then evaluates the treatment's safety and effectiveness. It suits those who have experienced some success with initial cancer treatments and maintain a stable health condition without major complications. Those who have responded well to atezolizumab and other treatments without severe side effects may find this an opportunity. As a Phase 1, Phase 2 trial, the research focuses on understanding how the treatment works in participants and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that quaratusugene ozeplasmid, when combined with atezolizumab, appears safe. One study found no serious side effects that would limit the dose, indicating that patients generally tolerated the treatment well, even at higher doses.

Atezolizumab alone has undergone extensive study and is considered safe for treating small cell lung cancer. Previous research indicates that atezolizumab, especially when combined with chemotherapy, is generally safe, with manageable side effects.

These findings suggest that using quaratusugene ozeplasmid with atezolizumab could be safe for patients. However, individual reactions may vary, so discussing participation in a trial with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about quaratusugene ozeplasmid for small cell lung cancer because it brings a fresh approach to treatment. Unlike standard therapies like chemotherapy and immunotherapy, quaratusugene ozeplasmid is a gene therapy delivered intravenously, designed to work alongside atezolizumab, an existing immunotherapy. This combination potentially enhances the immune system's ability to target and destroy cancer cells more effectively. Additionally, the gene therapy aspect might offer a novel mechanism of action by directly altering cancer cell behavior, which could lead to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for Small Cell Lung Cancer?

Research has shown that the combination of quaratusugene ozeplasmid and atezolizumab, which trial participants will receive, may improve outcomes for lung cancer patients. This combination extended the time during which the cancer did not worsen and led to partial remission in early studies. Quaratusugene ozeplasmid uses the TUSC2 gene to disrupt signals in cancer cells, potentially slowing cancer growth. Atezolizumab has already proven effective in treating extensive-stage small cell lung cancer (ES-SCLC) by extending patient survival when combined with chemotherapy. Together, these treatments show promise for better control of lung cancer progression. ^{2 3 5 6 7}

Who Is on the Research Team?

Mark S Berger, MD

Principal Investigator

Genprex, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with Extensive Stage Small Cell Lung Cancer who've had a stable heart condition, responded well to initial cancer therapy without severe side effects, and have good physical functioning. They should not have recent major surgeries or active complications from past surgeries. Brain metastases must be treated and stable. Blood counts and organ functions need to be within certain limits.

Inclusion Criteria

My kidney function is good, with creatinine levels at or below 1.5 mg/dL.

My small cell lung cancer was confirmed by lab tests before starting treatment with atezolizumab, carboplatin, and etoposide.

My blood tests show enough neutrophils and platelets.

Exclusion Criteria

I have not had a heart attack or unstable chest pain in the last 6 months.

I have undergone gene therapy before.

I am currently being treated for a serious infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Selection (Phase 1)

Participants receive quaratusugene ozeplasmid and atezolizumab to determine the recommended Phase 2 dose (RP2D)

21 days per dose level

IV administration once every 21 days

Safety and Efficacy Evaluation (Phase 2)

Participants are treated with the RP2D of quaratusugene ozeplasmid and atezolizumab until disease progression or unacceptable toxicity

18 weeks

IV administration once every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 5 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Quaratusugene Ozeplasmid

Trial Overview The trial is testing quaratusugene ozeplasmid (Reqorsa) combined with atezolizumab as a maintenance treatment after initial success with chemotherapy in ES-SCLC patients. It's done in two parts: first to find the right dose and second to check how safe and effective it is.

How Is the Trial Designed?

Group I: Phase 2 Experimental Treatment 2 Interventions

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

Group II: Phase 1 Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

Genprex, Inc.

Lead Sponsor

Trials

4

Recruited

250+

Published Research Related to This Trial

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

Atezolizumab is being studied as a neoadjuvant treatment for muscle-invasive bladder cancer (MIBC) in a phase II trial, where it is administered before radical cystectomy to evaluate its effectiveness based on the BASQ classification of tumor subtypes.

The trial aims to determine the objective pathological responses and 1-year progression-free survival rates in patients with MIBC, highlighting the potential of using molecular subtype characteristics to select the most responsive patient groups for atezolizumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of neoadjuvant atezolizumab treatment in patients with advanced urothelial bladder cancer according to the BASQ classification: a study protocol for an open-label, two-cohort, phase II trial. Yuk, HD., Jeong, CW., Kwak, C., et al.[2021]

The addition of atezolizumab to chemotherapy for extensive-stage small-cell lung cancer resulted in significantly higher costs ($48,129) compared to chemotherapy alone ($12,920), but only a marginal increase in quality-adjusted life-years (0.072 QALYs).

The cost-effectiveness ratio for atezolizumab plus chemotherapy was $489,013 per QALY, indicating it is not cost-effective compared to chemotherapy alone at the willingness-to-pay threshold of $25,929 per QALY in China.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line atezolizumab plus chemotherapy in treatment of extensive small cell lung cancer: a cost-effectiveness analysis from China. Li, LY., Wang, H., Chen, X., et al.[2023]

Atezolizumab is the first approved anti-PD-L1 inhibitor for treating squamous cell lung cancer (SqCLC) in patients who have experienced disease progression after initial therapies, highlighting its role in advanced stages of non-small cell lung cancer (NSCLC).

Current research is exploring atezolizumab's effectiveness in various treatment settings for SqCLC, indicating its potential for broader applications in future clinical scenarios, although specific target agents for this cancer subtype remain limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti PD-L1 antibody: is there a histologic-oriented efficacy? Focus on atezolizumab in squamous cell non-small cell lung cancer. Gemelli, M., Bidoli, P., Colonese, F., et al.[2022]

In a study of 47 patients with transformed small-cell lung cancer (T-SCLC), combining the PD-L1 inhibitor atezolizumab with chemotherapy resulted in a high objective response rate of 73% and significantly improved overall survival (20.2 months) compared to those who did not receive immunotherapy (7.9 months).

The combination therapy was well tolerated, showing a safety profile consistent with previous studies, suggesting it could be a promising treatment option for T-SCLC patients, particularly those with positive PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival. Zhang, CY., Sun, H., Su, JW., et al.[2023]

In a study of 115 patients with metastatic urothelial carcinoma treated with atezolizumab (ATZ) after failing first-line chemotherapy, the objective response rate was 28.7%, indicating that ATZ is effective in this patient population.

The treatment was well tolerated, with 98% of patients experiencing adverse events, but only 21.2% had severe (grade 3-4) treatment-related adverse events, suggesting a manageable safety profile similar to previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. Tural, D., Ölmez, ÖF., Sümbül, AT., et al.[2022]

Atezolizumab treatment in 615 patients with previously treated advanced non-small cell lung cancer showed a median overall survival of 11.1 months and a median progression-free survival of 2.7 months, indicating its efficacy in this population.

The safety profile was manageable, with treatment-related serious adverse events occurring in 7.8% of patients and immune-related adverse events in 8.3%, confirming that atezolizumab can be safely administered even to patients with severe renal impairment and other challenging conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary results from TAIL: a global single-arm safety study of atezolizumab monotherapy in a diverse population of patients with previously treated advanced non-small cell lung cancer. Ardizzoni, A., Azevedo, S., Rubio-Viqueira, B., et al.[2021]

Atezolizumab significantly improves overall survival (OS) and progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, based on a meta-analysis of 7 randomized clinical trials involving 4,859 patients.

The effectiveness of atezolizumab varies based on clinical and molecular features, with better outcomes observed in younger patients, those with wild-type EGFR, and active or previous smokers, highlighting the importance of personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Atezolizumab for Advanced Non-Small Cell Lung Cancer Based on Clinical and Molecular Features: A Meta-Analysis. Liu, W., Huo, G., Chen, P.[2022]

In a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

Atezolizumab combined with carboplatin and etoposide was effective in treating a 75-year-old woman with advanced small cell lung cancer and an ECOG Performance Status of 2, leading to complete regression after 4 cycles of treatment.

Despite experiencing some adverse effects like anemia and thrombocytopenia, the patient's therapy was continued due to positive imaging results, highlighting the potential for immunochemotherapy in patients typically excluded from clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 75-Year-Old Female Smoker with Advanced Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status 2 who Responded to Combination Immunochemotherapy with Atezolizumab, Etoposide, and Carboplatin. Dębczyński, M., Mojsak, D., Kuklińska, B., et al.[2022]

In a study involving 69 pediatric patients and 18 young adults, atezolizumab showed a similar safety profile across both age groups, indicating that weight-based dosing for children is appropriate.

Pharmacokinetic analysis revealed that while pediatric patients had about 20% lower drug exposure compared to young adults, both groups achieved the target drug concentration, suggesting effective dosing strategies for treating metastatic solid tumors or hematologic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics, exposure-safety, and immunogenicity of atezolizumab in pediatric and young adult patients with cancer. Shemesh, CS., Chanu, P., Jamsen, K., et al.[2023]

In the IMpower133 study involving 394 patients with extensive-stage small-cell lung cancer, the addition of atezolizumab to carboplatin and etoposide significantly improved progression-free and overall survival without increasing the overall safety risks compared to the placebo.

While immune-related adverse events were more common in the atezolizumab group, the overall safety profile was comparable to the placebo, and patient-reported quality of life improved more significantly in the atezolizumab group, supporting its use as a new standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial. Mansfield, AS., Każarnowicz, A., Karaseva, N., et al.[2022]

In a retrospective study of 213 patients with extensive-stage small cell lung cancer (SCLC), atezolizumab combined with chemotherapy demonstrated a median progression-free survival (PFS) of 6.8 months and overall survival (OS) of 11.9 months, confirming its efficacy in a real-life setting.

The treatment was generally safe, with manageable hematological side effects, and factors like ECOG performance status and number of metastatic sites were found to influence both PFS and OS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: a real-life data of the Turkish Oncology Group. Gürbüz, M., Kutlu, Y., Akkuş, E., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12563583/

Effectiveness of Atezolizumab in Addition to Chemotherapy in ... Atezolizumab showed effectiveness and manageable safety consistent with clinical trials, supporting its use in routine ES-SCLC treatment.

2. tecentriq-hcp.com tecentriq-hcp.com/sclc/efficacy/clinical-trial-results.html

IMpower133 efficacy results in 1L ES-SCLC Adding TECENTRIQ® (atezolizumab) to carbo/etop significantly improved median PFS1. 5.2-month median PFS vs 4.3 months with placebo + carbo/etop (HR=0.77*; ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1809064

First-Line Atezolizumab plus Chemotherapy in Extensive- ... Despite response rates of 60 to 65%, limited progress has been made in more than two decades; outcomes remain poor, with a median overall ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0169500223009170

Results of the IFCT-1905 CLINATEZO real-world study Atezolizumab plus chemotherapy improves overall survival in 1st-line treatment of extensive SCLC. IFCT-1905 CLINATEZO studied consecutive patients receiving ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37871898/

The Real-World Outcome of First Line Atezolizumab in ... We provided evidence of the favorable real-world effectiveness and safety of atezolizumab plus chemotherapy in ES-SCLC patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11880126/

Efficacy and safety analysis of atezolizumab continuation ... The IMpower 133 trial demonstrated that combining atezolizumab with chemotherapy significantly enhanced survival, establishing chemo-immunotherapy as the ...

7. tecentriq.com tecentriq.com/sclc/results/how-tecentriq-may-help.html

Imagine if you had more time to live your life Median overall survival (OS) was 12.3 months for patients taking TECENTRIQ® (atezolizumab. Patients who received TECENTRIQ with chemotherapy† had a 30% reduced ...