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

Overview

The goal of this Phase 3 clinical trial is to 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 630 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 on squamous cell NSCLC. Patients will be randomized 1:1 to receive either gotistobart at the selected dosing regimen or docetaxel.

Interventions

• Drug Gotistobart
  Gotistobart will be administrated through IV infusion over 60 minutes, once every 21 days in assigned dose.
• Drug Docetaxel
  Docetaxel will be administrated through IV infusion over 60 minutes, once every 21 days in 75mg/m2 dose.

Primary outcome measures

• Overall Survival (OS) [Time frame: 36 months]

Secondary outcome measures (3)

• Objective response rate (ORR) [Time frame: 36 months]
• Progression-free survival (PFS) [Time frame: 36 months]
• Treatment emergent adverse events, treatment related adverse events and immune related adverse events. [Time frame: 36 months]

Eligibility criteria

Inclusion Criteria (Major criteria):

• Adult (≥ 18 years), all genders, capable of signing informed consent.
• Histologically- or cytologically- confirmed diagnosis of metastatic squamous NSCLC, metastasis can be regional lymph nodes or distant organs.
• Radiographic progression after treatment with the most recent line of treatment being either 3a or 3b:

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

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

Exclusion Criteria (Major criteria):

• Cancer treatment related AEs have not recovered to NCI CTCAE grade≤ 1 except endocrinopathy.
• Last anti-PD-1/PD-L1 dosing within 28 days prior to first dose of study treatment.
• Receiving systemic steroid therapy with >10 mg/day prednisone or equivalent within 7 days prior to the first dose of study treatment.
• 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.
• Patients who have symptomatic brain metastasis. Palliative radiotherapy or radiosurgery to brain metastasis within 14 days of the first dose of study drug.
• Active GI disease, including peptic ulcer disease, pancreatitis, diverticulitis, or inflammatory bowel disease.
• Active interstitial lung disease (ILD) or non-infectious pneumonitis.
• Active infections with IV antibiotics within 14 days prior to first dose of study treatment.
• Impaired heart function.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 46 centers

• XCancer/Dothan Hematology & Oncology - 1114 — Dothan
• Genesis Cancer and Blood Institute - 1123 — Russellville
• The Oncology Institute (TOI) Clinical Research - 1109 — Cerritos
• Emad Ibrahim MD Inc. - 1147 — Redlands
• UC Davis Comprehensive Cancer Center - 1103 — Sacramento
• Bass Medical Group - 1155 — Walnut Creek
• Nuvance Health - 1118 — Norwalk
• D&H Cancer Research Center LLC - 1153 — Margate
• … and 38 more centers

China · 40 centers

• The First Affiliated Hospital of Anhui Medical University - 3221 — Hefei
• Anhui Medical University - The Second Hospital - 3222 — Hefei
• Beijing Cancer Hospital - 3205 — Beijing
• Cancer Hospital, Chinese Academy of Medical Sciences - 3211 — Beijing
• Fujian Medical University Union Hospital - 3225 — Fuzhou
• The First Affiliated Hospital of Xiamen University - 3210 — Xiamen
• Dongguan People's Hospital - 3206 — Dongguan
• Guangdong Provincial People's Hospital - 3201 — Guangzhou
• … and 32 more centers

Turkey (Türkiye) · 12 centers

Center list to be confirmed — check the primary protocol.

Italy · 11 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 10 centers

Center list to be confirmed — check the primary protocol.

South Korea · 7 centers

Center list to be confirmed — check the primary protocol.

Germany · 6 centers

Center list to be confirmed — check the primary protocol.

Spain · 6 centers

Center list to be confirmed — check the primary protocol.

Australia · 4 centers

• Bankstown Hospital - 3305 — Bankstown
• Mater - 3301 — Newstead
• Cancer Research SA - 3303 — Adelaide
• Western Health - Sunshine Hospital - 3307 — St Albans

Belgium · 4 centers

• AZ Maria Middelares - 2104 — Ghent
• Jessa Ziekenhuis (Jessa Hospital) - Campus Salvator - 2102 — Hasselt
• C. H. R. de la Citadelle - 2103 — Liège
• Vitaz - Sint-niklaas Moerland - 2101 — Sint-Niklaas

Canada · 3 centers

• BC Cancer Centre - Kelowna - 1203 — Kelowna
• Saskatchewan Cancer Agency - Regina - 1201 — Regina
• Saskatchewan Cancer Agency - Saskatoon Cancer Centre - 1202 — Saskatoon

Netherlands · 3 centers

Center list to be confirmed — check the primary protocol.

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. PMID 31267017
• 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. PMID 31836191
• Cho BC, Balaraman R, Chen HJ, Yu X, Fawole A, Liu ZG, Zhang J, Wu L, Yang B, Leddon JL, Hamm J, Huang Y, Wu L, Pan P, Singh P, Beardsley A, Kayali F, Davarifar A, Lee KH, Park KU, Lee Y, Li L, Wang X, Sun M, Yu Y, Jain V, Shpyro S, Wang Q, Wenger M, Sahin U, Efuni S, Song S, He K, Zheng P, Liu Y, He K, Li T, Socinski MA, Wu YL. Gotistobart or docetaxel in metastatic squamous non-small cell lung ca PMID 41896648

Identifiers

NCT: NCT05671510 · PRESERVE-003 · 2023-505311-20-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗