PRESERVE-003: Study of ONC-392 vs. Docetaxel in PD-1 Resistant Non-small Cell Lung Cancer
Study Details
Study Description
Brief Summary
The goal of this Phase 3 clinical trial is study the safety and efficacy of the nextgen anti-CTLA-4 antibody, ONC-392, 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 ONC-392, in comparison with chemotherapy agent Docetaxel, could prolong the life for NSCLC patients. Patients will be randomized to be treated with either ONC-392 or Docetaxel, IV infusion, once every 21 days, for up to 17 cycles in approximately one year.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
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 ONC-392 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 ONC-392 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 ONC-392 at the selected dosing regimen versus docetaxel. Patients will be randomized 1:1 to receive either ONC-392 at the selected dosing regimen or docetaxel.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1: ONC-392 6 mg/kg with 2 loading doses of 10 mg/kg, Q3W ONC-392 will be administrated by IV infusion in 60 minutes on day 1 of each cycle. A cycle is 21 days. |
Drug: ONC-392
ONC-392 will be administrated through IV infusion over 60 minutes, once every 21 days in assigned dose.
Other Names:
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| Experimental: Arm 2: ONC-392 3 mg/kg Q3W ONC-392 will be administrated by IV infusion in 60 minutes on day 1 of each cycle. A cycle is 21 days. |
Drug: ONC-392
ONC-392 will be administrated through IV infusion over 60 minutes, once every 21 days in assigned dose.
Other Names:
|
| 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. |
Drug: Docetaxel
Docetaxel will be administrated through IV infusion over 60 minutes, once every 21 days in 75mg/m2 dose.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [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.
Secondary Outcome Measures
- Objective response rate (ORR) [36 months]
Objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) per RECIST 1.1
- Progression-free survival (PFS) [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. [36 months]
Incidence of TEAEs, TRAEs, irAEs will be calcuated. The AEs leading to treatment discontinuation will be recorded.
Eligibility Criteria
Criteria
Inclusion Criteria (Major criteria):
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Adult (≥ 18 years), all genders, capable of signing informed consent.
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Histologically- or cytologically- confirmed diagnosis of metastatic NSCLC, metastasis can be regional lymph nodes or distant organs.
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Radiographic progression after treatment with the most recent line of treatment being either 3a or 3b:
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At least 12 weeks of PD-1/PD-L1 inhibitor in combination with platinum-based chemotherapy;
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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.
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At least one measurable tumor lesion according to RECIST 1.1.
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ECOG score of 0 or 1.
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Adequate organ functions. Serum LDH level ≤ 2xULN.
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Life expectancy ≥ 3 months.
Exclusion Criteria (Major criteria):
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Cancer treatment related AEs have not recovered to NCI CTCAE grade≤ 1 except endocrinopathy.
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Last anti-PD-1/PD-L1 dosing within 28 days prior to first dose of study treatment.
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Receiving systemic steroid therapy with >10 mg/day prednisone or equivalent within 7 days prior to the first dose of study treatment.
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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.
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Patients who have symptomatic brain metastasis. Palliative radiotherapy or radiosurgery to brain metastasis within 14 days of the first dose of study drug.
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Active GI disease, including peptic ulcer disease, pancreatitis, diverticulitis, or inflammatory bowel disease.
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Active interstitial lung disease (ILD) or non-infectious pneumonitis.
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Active infections with IV antibiotics within 14 days prior to first dose of study treatment.
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Impaired heart function.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California at Davis | Davis | California | United States | 95817 |
| 2 | AdventHealth Cancer Institute | Orlando | Florida | United States | 32804 |
| 3 | The Ohio State University James Cancer Center | Columbus | Ohio | United States | 43210 |
Sponsors and Collaborators
- OncoC4, Inc.
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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PRESERVE-003