Quaratusugene Ozeplasmid + Atezolizumab for Small Cell Lung Cancer

(Acclaim-3 Trial)

Recruiting at 11 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

Trial Summary

What is the purpose of this trial?

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).

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.

What data supports the effectiveness of the drug combination Quaratusugene Ozeplasmid + Atezolizumab for Small Cell Lung Cancer?

Atezolizumab, when combined with chemotherapy, has been shown to improve survival outcomes in patients with extensive-stage small cell lung cancer, as demonstrated in the IMpower133 trial. This combination was generally well tolerated and did not negatively impact patients' quality of life. ^{1 2 3 4 5}

What is known about the safety of Atezolizumab and Quaratusugene Ozeplasmid in humans?

Atezolizumab has been shown to have manageable safety in various studies for different types of cancer, including lung and bladder cancer. It has been evaluated in combination with other treatments and has been found to improve survival with a manageable safety profile in patients with small cell lung cancer. ^{6 7 8 9 10}

What makes the drug Quaratusugene Ozeplasmid + Atezolizumab unique for small cell lung cancer?

Quaratusugene Ozeplasmid (Reqorsa) combined with Atezolizumab is unique because it combines a novel gene therapy approach with an immune checkpoint inhibitor, potentially offering a new mechanism to enhance the immune system's ability to fight small cell lung cancer, which is different from traditional chemotherapy or single-agent immunotherapy. ^{1 11 12 13 14}

Research Team

Mark S Berger, MD

Principal Investigator

Genprex, Inc.

Eligibility Criteria

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.

I agree not to donate sperm during and for 4 months after the study.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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, 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]

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]

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 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]

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]

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]

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]

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]

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 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]

References

1. United States 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. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]

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

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

4. Ireland pubmed.ncbi.nlm.nih.gov

A potential treatment option for transformed small-cell lung cancer on PD-L1 inhibitor-based combination therapy improved survival. [2023]

5. China pubmed.ncbi.nlm.nih.gov

First-line atezolizumab plus chemotherapy in treatment of extensive small cell lung cancer: a cost-effectiveness analysis from China. [2023]

6. England 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. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Atezolizumab in Patients with Metastatic Urothelial Carcinoma Who Have Progressed After First-line Chemotherapy: Results of Real-life Experiences. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Population pharmacokinetics, exposure-safety, and immunogenicity of atezolizumab in pediatric and young adult patients with cancer. [2023]

9. England 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. [2022]

10. Germany 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. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of Atezolizumab for Advanced Non-Small Cell Lung Cancer Based on Clinical and Molecular Features: A Meta-Analysis. [2022]

12. England 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. [2021]

13. England 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. [2022]

14. Singapore 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. [2022]