ONC-392 Versus Docetaxel in Metastatic NSCLC That Progressed on PD-1/PD-L1 Inhibitors (PRESERVE-003)

• ClinicalTrials.gov Identifier: NCT05671510
• Recruitment Status: Recruiting
• First Posted: January 4, 2023
• Last Update Posted: May 10, 2024
• Sponsor: OncoC4, Inc.
• Collaborator: BioNTech SE
• Information provided by (Responsible Party): OncoC4, Inc.

Tracking Information

• First Submitted Date: December 26, 2022
• First Posted Date: January 4, 2023
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: June 28, 2023
• Estimated Primary Completion Date: June 30, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 31, 2022)

Overall Survival (OS) [ Time Frame: 36 months ]

OS is defined as the time from randomization to the date of death by any cause. Kaplan-Meier estimates of median OS time will be presented by treatment arm with two sided 95% CIs.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 31, 2022)

• Objective response rate (ORR) [ Time Frame: 36 months ]
  Objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) per RECIST 1.1
• Progression-free survival (PFS) [ Time Frame: 36 months ]
  Progression-free survival (PFS) as assessed by Investigator per RECIST 1.1
• Treatment emergent adverse events, treatment related adverse events and immune related adverse events. [ Time Frame: 36 months ]
  Incidence of TEAEs, TRAEs, irAEs will be calcuated. The AEs leading to treatment discontinuation will be recorded.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ONC-392 Versus Docetaxel in Metastatic NSCLC That Progressed on PD-1/PD-L1 Inhibitors
• Official Title: Phase 3, Two-stage, Randomized Study of ONC-392 Versus Docetaxel in Metastatic Non-Small Cell Lung Cancers That Progressed on PD-1/PD-L1 Inhibitors
• Brief Summary: The goal of this Phase 3 clinical trial is study the safety and efficacy of the nextgen anti-CTLA-4 antibody, gotistobart (ONC-392/BNT316), in patients with metastatic non-small cell lung cancer who have disease progressed on anti-PD-1/PD-L1 antibody based therapy. The study will test whether gotistobart, in comparison with chemotherapy agent docetaxel, could prolong the life for NSCLC patients. Patients will be randomized to be treated with either gotistobart or docetaxel, IV infusion, once every 21 days, for up to 17 cycles in approximately one year.

Detailed Description

This is a seamless 2-stage, randomized, open-label, active-controlled, Phase 3 study. The study population consists of patients with NSCLC who progressed on PD-1/PD-L1 inhibitor. Approximately 600 patients will be enrolled.

Two gotistobart dosing regimens will be tested in Stage I, and one will be selected for Stage II.

Stage I, the dose-confirmation stage, will assess the efficacy and safety of two gotistobart dosing regimens (3 mg/kg Q3W and 6 mg/kg Q3W with 2 loading doses of 10 mg/kg Q3W) in comparison to docetaxel 75 mg/m2 Q3W.

Stage II will assess the safety and efficacy of gotistobart at the selected dosing regimen versus docetaxel. Patients will be randomized 1:1 to receive either gotistobart at the selected dosing regimen or docetaxel.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized, open-label, active controlled, multi-center Phase 3 study.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Non Small Cell Lung Cancer

Intervention

• Drug: Gotistobart
  Gotistobart will be administrated through IV infusion over 60 minutes, once every 21 days in assigned dose.
  Other Names:

  • A humanized anti-CTLA4 IgG1 monoclonal antibody
  • ONC-392
  • BNT316
• Drug: Docetaxel
  Docetaxel will be administrated through IV infusion over 60 minutes, once every 21 days in 75mg/m2 dose.
  Other Names:

  • Docefrez
  • Taxotere

Study Arms

• Experimental: Arm 1: Gotistobart 6 mg/kg with 2 loading doses of 10 mg/kg, Q3W
  Gotistobart will be administrated by IV infusion in 60 minutes on day 1 of each cycle. A cycle is 21 days.
  Intervention: Drug: Gotistobart
• Experimental: Arm 2: Gotistobart 3 mg/kg Q3W
  Gotistobart will be administrated by IV infusion in 60 minutes on day 1 of each cycle. A cycle is 21 days.
  Intervention: Drug: Gotistobart
• Active Comparator: Arm 3: Docetaxel 75 mg/m2, Q3W
  Docetaxel will be administrated by IV infusion in 60 minutes on day 1 of each cycle. A cycle is 21 days.
  Intervention: Drug: Docetaxel

Publications *

• Zhang Y, Du X, Liu M, Tang F, Zhang P, Ai C, Fields JK, Sundberg EJ, Latinovic OS, Devenport M, Zheng P, Liu Y. Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy. Cell Res. 2019 Aug;29(8):609-627. doi: 10.1038/s41422-019-0184-1. Epub 2019 Jul 2.
• Liu Y, Zheng P. Preserving the CTLA-4 Checkpoint for Safer and More Effective Cancer Immunotherapy. Trends Pharmacol Sci. 2020 Jan;41(1):4-12. doi: 10.1016/j.tips.2019.11.003. Epub 2019 Dec 10.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 31, 2022): 600
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2027
• Estimated Primary Completion Date: June 30, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria (Major criteria):

1. Adult (≥ 18 years), all genders, capable of signing informed consent.
2. Histologically- or cytologically- confirmed diagnosis of metastatic NSCLC, metastasis can be regional lymph nodes or distant organs.

3. Radiographic progression after treatment with the most recent line of treatment being either 3a or 3b:

   1. At least 12 weeks of PD-1/PD-L1 inhibitor in combination with platinum-based chemotherapy;
   2. Prior treatment with at least 2 cycles of a platinum-based chemotherapy, followed by at least 12 weeks of standard doses of PD-1 or PD-L1 inhibitor-based immunotherapy.

   Antibodies against CTLA-4, LAG-3, TIGIT, VEGF or VEGFR in combination with PD-1/PD-L1 inhibitor are allowed.

4. At least one measurable tumor lesion according to RECIST 1.1.
5. ECOG score of 0 or 1.
6. Adequate organ functions. Serum LDH level ≤ 2xULN.
7. Life expectancy ≥ 3 months.

Exclusion Criteria (Major criteria):

1. Cancer treatment related AEs have not recovered to NCI CTCAE grade≤ 1 except endocrinopathy.
2. Last anti-PD-1/PD-L1 dosing within 28 days prior to first dose of study treatment.
3. Receiving systemic steroid therapy with >10 mg/day prednisone or equivalent within 7 days prior to the first dose of study treatment.
4. Having documented actionable mutations or genomic alterations in any of the following genes: EGFR, ALK, ROS1, HER2, MET, BRAF, RET or NTRK;. Exception: KRAS mutations are not excluded.
5. Patients who have symptomatic brain metastasis. Palliative radiotherapy or radiosurgery to brain metastasis within 14 days of the first dose of study drug.
6. Active GI disease, including peptic ulcer disease, pancreatitis, diverticulitis, or inflammatory bowel disease.
7. Active interstitial lung disease (ILD) or non-infectious pneumonitis.
8. Active infections with IV antibiotics within 14 days prior to first dose of study treatment.
9. Impaired heart function.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Pan Zheng, MD, PhD; 2027516823; pzheng@oncoc4.com

• Listed Location Countries: Australia, Belgium, Canada, China, France, Germany, Italy, Korea, Republic of, Netherlands, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT05671510
• Other Study ID Numbers: PRESERVE-003
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: OncoC4, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: OncoC4, Inc.
• Original Study Sponsor: Same as current
• Collaborators: BioNTech SE

Investigators

• Principal Investigator: Mark Socinski, MD; Advent Health System
• Principal Investigator: Tianhong Li, MD, PhD; University of California, Davis
• Principal Investigator: Kai He, MD, PhD; Ohio State University

• PRS Account: OncoC4, Inc.
• Verification Date: May 2024