ONC-392 vs Chemotherapy for Lung Cancer

(PRESERVE-003 Trial)

Recruiting at 264 trial locations

Overseen By Bo Wang, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: OncoC4, Inc.

Must not be taking: Systemic steroids

Disqualifiers: Symptomatic brain metastasis, Active infections, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called gotistobart (also known as ONC-392) for individuals with metastatic non-small cell lung cancer (NSCLC) who have not responded to other therapies. The researchers aim to determine if gotistobart can extend patients' lives compared to the standard chemotherapy drug, docetaxel. Participants will receive either gotistobart or docetaxel through an IV every 21 days for up to a year. Ideal candidates have experienced worsening lung cancer despite previous treatments with specific cancer-fighting drugs. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that gotistobart, a new treatment, may benefit people with certain lung cancers. Studies suggest that gotistobart is generally safe, with most patients tolerating it well.

In earlier research, when patients took gotistobart alone, side effects were usually mild and manageable. While some side effects might occur, they are typically not serious. For the doses tested (3 mg/kg and 6 mg/kg), the treatment was mostly safe, and many patients experienced positive outcomes.

Gotistobart is being compared to docetaxel, a chemotherapy drug familiar to doctors. Each treatment has its own possible side effects. However, the safety data for gotistobart appears promising, prompting further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for lung cancer, like chemotherapy with drugs such as Docetaxel, work by killing rapidly dividing cancer cells, but they can also affect healthy cells and cause significant side effects. Gotistobart, on the other hand, is unique because it is an experimental immunotherapy drug designed to enhance the body’s immune response specifically against cancer cells, potentially leading to fewer side effects. Researchers are excited about Gotistobart because it offers a new mechanism of action that could be more targeted and effective against lung cancer. With its different dosage options, Gotistobart could provide flexible treatment plans tailored to individual patient needs.

What evidence suggests that this trial's treatments could be effective for lung cancer?

This trial will compare Gotistobart with Docetaxel for treating lung cancer. Research has shown that Gotistobart, one of the treatments in this trial, delivers promising results in fighting cancer. Early studies found it safe and effective, especially for patients who no longer respond to other treatments. Gotistobart targets a protein called CTLA-4, which helps control the immune system. By doing this, it can help the body's immune system attack cancer cells more effectively. Initial findings suggest that Gotistobart may extend the lives of patients with advanced non-small cell lung cancer. While more research is needed, these early results offer hope for those seeking new treatment options. ^{1 2 5 6 7}

Who Is on the 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

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• ONC-392

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.

How Is the Trial Designed?

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 United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

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

Approved in European Union as Taxotere for:

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

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

Published Research Related to This Trial

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 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]

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 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]

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]

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]

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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05671510

NCT05671510 | ONC-392 Versus Docetaxel in Metastatic ... The study will test whether gotistobart, in comparison with chemotherapy agent docetaxel, could prolong the life for NSCLC patients.

2. investors.biontech.de investors.biontech.de/news-releases/news-release-details/biontech-and-oncoc4-initiate-pivotal-phase-3-trial-bnt316onc-392

BioNTech and OncoC4 Initiate Pivotal Phase 3 Trial of ... The initiation of the Phase 3 trial is based on positive safety and efficacy data from an ongoing Phase 1/2 study (NCT04140526) with BNT316/ONC- ...

3. oncoc4.com oncoc4.com/press-releases/oncoc4-to-present-global-pivotal-phase-3-trial-design-for-next-generation-ctla-4-antibody-gotistobart-monotherapy-being-co-developed-with-biontech-in-nsclc-at-the-iaslc-2025-world-conference-on-lung-c/

OncoC4 to Present Global Pivotal Phase 3 Trial Design ... PRESERVE-003 is evaluating gotistobart vs. docetaxel in patients with squamous non-small cell lung cancer (sqNSCLC) who have progressed on ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5067

Phase 1 study of gotistobart (BNT316/ONC-392) in ... gotistobart in combination with Lu 177 demonstrated a manageable safety profile and promising preliminary PSA50 rates in patients with mCRPC during the dose ...

5. graphite.ucsd.edu graphite.ucsd.edu/2025/05/04/onc-392-bnt-316gotistobart-a-new-promising-drug-for-cancer-patients/

ONC-392/BNT-316(Gotistobart) – a New Promising Drug ... Gotistobart is a new drug developed from cloning an antibody that exists within the body that targets the CTLA-4 that regulates and restricts T-Cell activation.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.9024

Safety and clinical activity of target-preserving anti-CTLA-4 ... Overall, ONC-392 monotherapy with 10 mg/kg is safe and tolerable. Onc-392 monotherapy has showed encouraging anti-tumor activity in IO-resistant NSCLC.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04140526

NCT04140526 | Safety, PK and Efficacy of ONC-392 in ... This is a First-in-Human Phase IA/IB/II open label dose escalation study of intravenous (IV) administration of ONC-392, a humanized anti-CTLA4 IgG1 monoclonal ...