ONC-392 vs Chemotherapy for Lung Cancer

(PRESERVE-003 Trial)

Recruiting in Palo Alto (17 mi)

+242 other locations

Overseen by Kai He, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: OncoC4, Inc.

Must not be taking: Systemic steroids

Disqualifiers: Symptomatic brain metastasis, Active infections, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing gotistobart, a new drug that helps the immune system fight advanced lung cancer in patients who haven't responded to other treatments. It works by blocking a protein that allows cancer cells to hide from the immune system.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on systemic steroid therapy with more than 10 mg/day prednisone or equivalent within 7 days before starting the study treatment.

What data supports the effectiveness of the drug Gotistobart for lung cancer?

Research shows that docetaxel, a component of Gotistobart, is effective in treating advanced non-small cell lung cancer, improving survival and quality of life for patients who have not responded to other chemotherapy treatments. ^{1 2 3 4 5}

Is Gotistobart (Docetaxel) generally safe for humans?

Docetaxel, also known as Gotistobart, has been used in various cancer treatments and is generally considered safe, though it can cause side effects like neutropenia (low white blood cell count) and fluid retention. These side effects are usually manageable with medications and monitoring. ^{6 7 8 9 10}

What makes the drug Gotistobart (Docetaxel) unique for lung cancer treatment?

Gotistobart, also known as Docetaxel, is unique because it is a semisynthetic taxane that has shown effectiveness in treating advanced non-small cell lung cancer, both as a single agent and in combination with other therapies. It is particularly noted for its ability to improve quality of life and modestly extend survival in patients who have not responded to other chemotherapy treatments. ^{1 2 3 11 12}

Research Team

Mark Socinski, MD

Principal Investigator

Advent Health System

Tianhong Li

Principal Investigator

University of California, Davis

Kai He, MD, PhD

Principal Investigator

Ohio State University

Eligibility Criteria

This trial is for adults with metastatic non-small cell lung cancer (NSCLC) who have already tried PD-1/PD-L1 inhibitors and chemotherapy. Patients whose disease has worsened after treatment are eligible to participate.

Inclusion Criteria

Histologically- or cytologically- confirmed diagnosis of metastatic NSCLC, metastasis can be regional lymph nodes or distant organs

My cancer has worsened after my last treatment.

At least 12 weeks of PD-1/PD-L1 inhibitor in combination with platinum-based chemotherapy

Exclusion Criteria

Active GI disease, including peptic ulcer disease, pancreatitis, diverticulitis, or inflammatory bowel disease.

I last received anti-PD-1/PD-L1 treatment less than 28 days ago.

I have not taken more than 10 mg/day of steroids like prednisone in the last week.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Stage I

Dose-confirmation stage assessing efficacy and safety of two gotistobart dosing regimens compared to docetaxel

21 weeks

1 visit every 3 weeks (in-person)

Treatment Stage II

Assessment of safety and efficacy of selected gotistobart dosing regimen versus docetaxel

21 weeks

1 visit every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Treatment Details

Interventions

• Docetaxel (Anti-tumor antibiotic)
• ONC-392 (Monoclonal Antibodies)

Trial Overview The study compares ONC-392, a new anti-CTLA-4 antibody, against docetaxel, a chemotherapy drug. The purpose of this study is to determine whether the study drug, ONC-392, is safe and well tolerated. The study will also test whether ONC-392 is effective in treating non-small call lung cancer, in comparison with the chemotherapy standard of care drug, docetaxel.

Participant Groups

Group I: Arm 2: Gotistobart 3 mg/kg Q3W Experimental Treatment 1 Intervention

Gotistobart will be administrated by IV infusion in 60 minutes on day 1 of each cycle. A cycle is 21 days.

Group II: Arm 1: Gotistobart 6 mg/kg with 2 loading doses of 10 mg/kg, Q3W Experimental Treatment 1 Intervention

Gotistobart will be administrated by IV infusion in 60 minutes on day 1 of each cycle. A cycle is 21 days.

Group III: Arm 3: Docetaxel 75 mg/m2, Q3W Active Control 1 Intervention

Docetaxel will be administrated by IV infusion in 60 minutes on day 1 of each cycle. A cycle is 21 days.

Docetaxel is already approved in Canada, Japan for the following indications:

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

OncoC4, Inc.

Lead Sponsor

Trials

8

Recruited

1,800+

BioNTech SE

Industry Sponsor

Trials

84

Recruited

120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Findings from Research

Docetaxel has been shown to improve quality of life and provide a modest prolongation of survival in patients with recurrent or metastatic non-small-cell lung cancer (NSCLC).

Randomized trials indicate that single-agent docetaxel is more effective than best supportive care for advanced NSCLC, benefiting both untreated patients and those who have previously undergone cisplatin-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-agent docetaxel (Taxotere) in the treatment of advanced non small-cell lung cancer: clinical concepts and commentary. Laurie, SA., Kris, MG.[2019]

Docetaxel has been established as the preferred treatment for advanced non-small cell lung cancer that does not respond to initial chemotherapy, based on the results of two recent trials.

Ongoing trials are exploring the use of docetaxel not only as a primary treatment but also in combination with radiation therapy, indicating its potential versatility in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer: an international update. Kris, MG., Manegold, C.[2019]

Docetaxel has been established as the preferred treatment for advanced non-small cell lung cancer that does not respond to initial chemotherapy, based on the results of two recent trials.

Ongoing trials are exploring the use of docetaxel not only as a primary treatment but also in combination with radiation therapy, indicating its potential versatility in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer: An international update. Kris, MG., Manegold, C.[2019]

Taxanes, such as paclitaxel and docetaxel, are effective chemotherapeutic agents for non-small cell lung cancer (NSCLC), showing significant anticancer activity in both single-agent and combination therapies, particularly with platinum compounds.

Docetaxel is not only effective as a first-line treatment for advanced NSCLC but is also FDA-approved as a second-line treatment for recurrent or relapsed cases, highlighting its importance in the management of this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxanes for advanced non-small cell lung cancer. Ramalingam, S., Belani, CP.[2019]

In a study of 104 patients with advanced non-small-cell lung cancer previously treated with platinum-based chemotherapy, treatment with docetaxel significantly prolonged median survival (7.0 months) compared to best supportive care (4.6 months).

The lower dose of docetaxel (75 mg/m²) was particularly effective, showing a median survival of 7.5 months and a 1-year survival rate of 37%, while also demonstrating manageable toxicity levels, making it a safer option compared to the higher dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. Shepherd, FA., Dancey, J., Ramlau, R., et al.[2023]

Docetaxel shows significant efficacy in treating advanced non-small cell lung cancer, with a 30% partial response rate in chemotherapy-naive patients and 20% in those who had previously failed platinum-based treatments, based on six phase II studies involving 268 patients.

The primary side effect of docetaxel is neutropenia, while fluid retention is common but usually manageable with corticosteroids, indicating that the treatment has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Summary of phase II data of docetaxel (Taxotere), an active agent in the first- and second-line treatment of advanced non-small cell lung cancer. Fossella, FV., Lee, JS., Berille, J., et al.[2018]

Docetaxel is an effective treatment for non-small cell lung cancer (NSCLC), showing comparable efficacy to newer platinum-based therapies in advanced stages, and has been approved for use in this context.

Clinical trials are ongoing to explore the best ways to combine docetaxel with other treatments, such as thoracic radiotherapy and molecularly targeted agents, to enhance its effectiveness in various stages of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel in non-small cell lung cancer: a review. Davies, AM., Lara, PN., Mack, PC., et al.[2019]

In a study of 27 patients with inoperable non-small-cell lung cancer (NSCLC) who had previously received platinum-based chemotherapy, docetaxel showed a partial response rate of 24%, indicating its effectiveness as a treatment option.

The main side effect observed was severe neutropenia in 75% of patients, highlighting the need for careful monitoring of blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of docetaxel in non-small cell lung cancer patients previously treated with platinum-containing chemotherapy. French Group of Pneumo-Cancerology]. Robinet, G., Thomas, P., Pérol, M., et al.[2018]

The combination of docetaxel and carboplatin as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) showed an overall response rate of 26.6%, with a median overall survival of 9 months based on a study of 38 patients.

While the treatment was generally well-tolerated, it did lead to significant hematological toxicity, particularly grade 3-4 neutropenia in 50% of patients, though there were no septic deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter phase II study of docetaxel and carboplatin combination as front-line treatment in advanced non-small cell lung cancer. Giannakakis, T., Kakolyris, S., Theodoropoulos, E., et al.[2018]

In a study of 1,006 patients, docetaxel combined with prednisone showed a significant overall survival advantage compared to mitoxantrone plus prednisone, with a median survival of 18.9 months versus 16.5 months.

The most common side effects of docetaxel included anemia, neutropenia, and nausea, indicating that while effective, the treatment does come with notable adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approval summary: Docetaxel in combination with prednisone for the treatment of androgen-independent hormone-refractory prostate cancer. Dagher, R., Li, N., Abraham, S., et al.[2018]

Docetaxel, when combined with other agents like cisplatin and gemcitabine, shows promising response rates (up to 53%) and median survival times (8 to 13 months) in patients with non-small-cell lung cancer, based on multiple phase I and II trials.

The combinations of docetaxel with other treatments have manageable adverse effects, making them a viable option for patients, with ongoing phase III trials to further evaluate their effectiveness in first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel (Taxotere) in combination chemotherapy and in association with thoracic radiotherapy for the treatment of non-small-cell lung cancer. Thoracic Oncology Program. Ornstein, DL., Nervi, AM., Rigas, JR.[2022]

Paclitaxel or docetaxel combined with cisplatin is recommended as an effective first-line treatment for advanced non-small cell lung cancer, showing a statistically significant survival advantage compared to best supportive care alone in two phase III trials.

While taxane-platinum combinations generally achieved higher response rates than older chemotherapy regimens, significant survival benefits were primarily observed with docetaxel-cisplatin compared to vinorelbine-cisplatin, indicating that specific combinations may offer better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxanes as first-line therapy for advanced non-small cell lung cancer: a systematic review and practice guideline. Chu, Q., Vincent, M., Logan, D., et al.[2022]

References

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

Single-agent docetaxel (Taxotere) in the treatment of advanced non small-cell lung cancer: clinical concepts and commentary. [2019]

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

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer: an international update. [2019]

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

Docetaxel (Taxotere) in the treatment of non-small cell lung cancer: An international update. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Taxanes for advanced non-small cell lung cancer. [2019]

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

Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. [2023]

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

Summary of phase II data of docetaxel (Taxotere), an active agent in the first- and second-line treatment of advanced non-small cell lung cancer. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Docetaxel in non-small cell lung cancer: a review. [2019]

8. France pubmed.ncbi.nlm.nih.gov

[Efficacy of docetaxel in non-small cell lung cancer patients previously treated with platinum-containing chemotherapy. French Group of Pneumo-Cancerology]. [2018]

9. Greece pubmed.ncbi.nlm.nih.gov

A multicenter phase II study of docetaxel and carboplatin combination as front-line treatment in advanced non-small cell lung cancer. [2018]

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

Approval summary: Docetaxel in combination with prednisone for the treatment of androgen-independent hormone-refractory prostate cancer. [2018]

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

Docetaxel (Taxotere) in combination chemotherapy and in association with thoracic radiotherapy for the treatment of non-small-cell lung cancer. Thoracic Oncology Program. [2022]

12. Ireland pubmed.ncbi.nlm.nih.gov

Taxanes as first-line therapy for advanced non-small cell lung cancer: a systematic review and practice guideline. [2022]