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

NCT05671510 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: PRESERVE-0032023-505311-20-01
• Study Type: interventional
• Target: 630
• Locations: 12 countries
• Sites: 152

Brief Summary

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.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  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.

  36 months

Secondary Outcomes (3)

• Objective response rate (ORR)

  36 months

• Progression-free survival (PFS)

  36 months

• Treatment emergent adverse events, treatment related adverse events and immune related adverse events.

  36 months

Study Arms (2)

Arm 1: Gotistobart 6 mg/kg with 2 loading doses of 10 mg/kg, Q3W

EXPERIMENTAL

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

Drug: Gotistobart

Arm 2: Docetaxel 75 mg/m2, Q3W

ACTIVE COMPARATOR

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

Drug: Docetaxel

Interventions

Gotistobart DRUG

Gotistobart will be administrated through IV infusion over 60 minutes, once every 21 days in assigned dose.

Also known as: A humanized anti-CTLA4 IgG1 monoclonal antibody, ONC-392, BNT316

Arm 1: Gotistobart 6 mg/kg with 2 loading doses of 10 mg/kg, Q3W

Docetaxel DRUG

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

Also known as: Docefrez, Taxotere

Arm 2: Docetaxel 75 mg/m2, Q3W

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• OncoC4, Inc.: lead
• BioNTech SE: collaborator

Study Sites (152)

XCancer/Dothan Hematology & Oncology - 1114

Dothan, Alabama, 36303, United States

RECRUITING

Genesis Cancer and Blood Institute - 1123

Russellville, Arkansas, 72801, United States

RECRUITING

The Oncology Institute (TOI) Clinical Research - 1109

Cerritos, California, 90703, United States

RECRUITING

Emad Ibrahim MD Inc. - 1147

Redlands, California, 92373, United States

RECRUITING

UC Davis Comprehensive Cancer Center - 1103

Sacramento, California, 95817, United States

RECRUITING

Bass Medical Group - 1155

Walnut Creek, California, 94598, United States

RECRUITING

Nuvance Health - 1118

Norwalk, Connecticut, 06850, United States

RECRUITING

D&H Cancer Research Center LLC - 1153

Margate, Florida, 33063, United States

RECRUITING

Ocala Oncology Center PL - 1102

Ocala, Florida, 34474, United States

RECRUITING

AdventHealth Cancer Institute - 1105

Orlando, Florida, 32804, United States

RECRUITING

Orlando Health - 1130

Orlando, Florida, 32806, United States

RECRUITING

Florida Cancer Specialists -South - 1126

Sarasota, Florida, 34232, United States

RECRUITING

Florida Cancer Specialists -North - 1125

The Villages, Florida, 32159, United States

RECRUITING

Florida Cancer Specialists -East - 1124

West Palm Beach, Florida, 33401, United States

RECRUITING

Orchard Healthcare Research, Inc. - 1116

Skokie, Illinois, 60077, United States

RECRUITING

Springfield Clinic - The Cancer Center - 1110

Springfield, Illinois, 62702, United States

RECRUITING

Fort Wayne Medical Oncology - 1133

Fort Wayne, Indiana, 46805, United States

RECRUITING

Deaconess Chancellor Center for Oncology - 1131

Newburgh, Indiana, 47630, United States

RECRUITING

Cotton O'Neil Clinical Research Center - 1151

Topeka, Kansas, 66606, United States

RECRUITING

University of Kentucky - Markey Cancer Center - 1112

Lexington, Kentucky, 40536, United States

RECRUITING

Norton Cancer Institute - 1108

Louisville, Kentucky, 40202, United States

RECRUITING

Jefferson City Medical Group - 1145

Jefferson City, Missouri, 65109, United States

RECRUITING

MidAmerica Cancer Care - 1163

Kansas City, Missouri, 64132, United States

RECRUITING

Astera Cancer Care - 1128

East Brunswick, New Jersey, 08816, United States

RECRUITING

Duke University Medical Center - 1158

Durham, North Carolina, 27710, United States

RECRUITING

Miami Valley Hospital - 1115

Centerville, Ohio, 45459, United States

RECRUITING

University of Cincinnati Cancer Center - 1107

Cincinnati, Ohio, 45219, United States

RECRUITING

The Ohio State University James Cancer Center - 1104

Columbus, Ohio, 43210, United States

RECRUITING

Tri County Hematology & Oncology Associates, Inc - 1156

Massillon, Ohio, 44646, United States

RECRUITING

Oklahoma Cancer Specialists and Research Institute - 1154

Tulsa, Oklahoma, 74146, United States

RECRUITING

Oncology Associates of Oregon - 1138

Eugene, Oregon, 97401, United States

RECRUITING

St. Luke's University Health Network - 1179

Bethlehem, Pennsylvania, 18015, United States

RECRUITING

Donald Guthrie Foundation - 1135

Sayre, Pennsylvania, 18840, United States

RECRUITING

Cancer Care Associates of York, Inc. - 1113

York, Pennsylvania, 17403, United States

RECRUITING

University of Tennessee Medical Center - 1146

Knoxville, Tennessee, 37920, United States

RECRUITING

Sarah Cannon Research Institute - Tennessee Oncology at Nashville - 1119

Nashville, Tennessee, 37203, United States

RECRUITING

Texas Oncology - Baylor Charles A. Sammons Cancer Center (USOR) - 1140

Dallas, Texas, 75246, United States

RECRUITING

Texas Oncology - Denison - 1139

Denison, Texas, 75020, United States

RECRUITING

Oncology Consultants, P.A. - 1120

Houston, Texas, 77024, United States

RECRUITING

Oncology and Hematology of South Texas - 1165

Laredo, Texas, 78041, United States

RECRUITING

Texas Oncology - McAllen - 1132

McAllen, Texas, 78503, United States

RECRUITING

Texas Oncology -San Antonio - 1122

San Antonio, Texas, 78240, United States

RECRUITING

NEXT Oncology - Virginia - 1129

Fairfax, Virginia, 22031, United States

RECRUITING

Virginia Cancer Institute - 1149

Henrico, Virginia, 23226, United States

RECRUITING

Virginia Oncology Associates - 1136

Norfolk, Virginia, 23502, United States

RECRUITING

West Virginia University Cancer Institute - 1172

Morgantown, West Virginia, 26505, United States

RECRUITING

Bankstown Hospital - 3305

Bankstown, New South Wales, 2200, Australia

NOT YET RECRUITING

Mater - 3301

Newstead, Queensland, 4006, Australia

NOT YET RECRUITING

Cancer Research SA - 3303

Adelaide, South Australia, 5000, Australia

COMPLETED

Western Health - Sunshine Hospital - 3307

St Albans, Victoria, 3021, Australia

NOT YET RECRUITING

AZ Maria Middelares - 2104

Ghent, 9000, Belgium

RECRUITING

Jessa Ziekenhuis (Jessa Hospital) - Campus Salvator - 2102

Hasselt, 3500, Belgium

RECRUITING

C. H. R. de la Citadelle - 2103

Liège, 4000, Belgium

RECRUITING

Vitaz - Sint-niklaas Moerland - 2101

Sint-Niklaas, 9100, Belgium

RECRUITING

BC Cancer Centre - Kelowna - 1203

Kelowna, British Columbia, Canada

RECRUITING

Saskatchewan Cancer Agency - Regina - 1201

Regina, Saskatchewan, S4T 7T1, Canada

RECRUITING

Saskatchewan Cancer Agency - Saskatoon Cancer Centre - 1202

Saskatoon, Saskatchewan, S7N 4H4, Canada

RECRUITING

The First Affiliated Hospital of Anhui Medical University - 3221

Hefei, Anhui, 230022, China

COMPLETED

Anhui Medical University - The Second Hospital - 3222

Hefei, Anhui, 231200, China

COMPLETED

Beijing Cancer Hospital - 3205

Beijing, Beijing Municipality, China

COMPLETED

Cancer Hospital, Chinese Academy of Medical Sciences - 3211

Beijing, Beijing Municipality, China

COMPLETED

Fujian Medical University Union Hospital - 3225

Fuzhou, Fujian, China

COMPLETED

The First Affiliated Hospital of Xiamen University - 3210

Xiamen, Fujian, China

COMPLETED

Dongguan People's Hospital - 3206

Dongguan, Guangdong, China

COMPLETED

Guangdong Provincial People's Hospital - 3201

Guangzhou, Guangdong, 510105, China

COMPLETED

Zhujiang Hospital of Southern Medical University - 3203

Guangzhou, Guangdong, 510280, China

COMPLETED

The First Affiliated Hospital of Guangdong Pharmaceutical University - 3215

Guangzhou, Guangdong, China

COMPLETED

The People's Hospital of Guangxi Zhuang Autonomous Region - 3228

Nanning, Guangxi, 530021, China

COMPLETED

Hainan General Hospital - 3202

Haikou, Hainan, China

COMPLETED

Affiliated Hospital of Hebei University - 3214

Zhengzhou, Hebei, 71000, China

COMPLETED

The Affiliated Tumor Hospital of Harbin Medical University - 3232

Harbin, Heilongjiang, 150040, China

COMPLETED

Henan Cancer Hospital - 3226

Zhengzhou, Henan, 450008, China

COMPLETED

The First Affliated Hospital of Zhengzhou University - 3207

Zhengzhou, Henan, China

COMPLETED

Renmin Hospital of Wuhan University - 3216

Wuhan, Hubei, China

COMPLETED

Union Hospital Tongji Medical College - 3212

Wuhan, Hubei, China

COMPLETED

Xiangya Hospital, Central South University - 3223

Changsha, Hunan, 410008, China

COMPLETED

Hunan Cancer Hospital - 3209

Changsha, Hunan, China

COMPLETED

The Second Affiliated Hospital of Soochow University - 3217

Suzhou, Jiangsu, China

COMPLETED

Xuzhou Medical University - The Affiliated Hospital - 3234

Xuzhou, Jiangsu, 221002, China

COMPLETED

The Second Affiliated Hospital of Nanchang University - 3224

Nanchang, Jiangxi, 330006, China

COMPLETED

Jinan Central Hospital - 3230

Jinan, Shandong, 250013, China

COMPLETED

Shanxi Bethune Hospital - 3233

Taiyuan, Shanxi, 30032, China

COMPLETED

The First Affiliated Hospital of Xi'an Jiaotong University - 3218

Xi’an, Shanxi, China

COMPLETED

Chengdu Seventh People's Hospital - 3229

Chengdu, Sichuan, 610041, China

COMPLETED

Sichuan Cancer Hospital - 3227

Chengdu, Sichuan, 610041, China

COMPLETED

Chongqing University Cancer Hospital - 3213

Chongqing, Sichuan, China

COMPLETED

Tianjin Medical University Cancer Institute and Hospital - 3208

Tianjin, Tianjin Municipality, China

COMPLETED

Yunnan Cancer Hospital - 3231

Kunming, Yunnan, 650118, China

COMPLETED

Sir Run Run Shaw Hospital, Zhejiang University School of Medicine - 3219

Hangzhou, Zhejiang, China

COMPLETED

The Second Affiliated Hospital of Zhejiang University School of Medicine - 3220

Hangzhou, Zhejiang, China

COMPLETED

Zhejiang Cancer Hospital - 3204

Hangzhou, Zhejiang, China

COMPLETED

China-Japan Friendship Hospital - 3236

Beijing, 100029, China

COMPLETED

West China Hospital, Sichuan University - 3238

Chengdu, 610041, China

COMPLETED

Nanjing Medical University (NMU) - Nanjing First Hospital - 3239

Jiangse, 21006, China

COMPLETED

Weifang Second People's Hospital - 3235

Shandong, 261041, China

COMPLETED

Tongji University - Shanghai Oriental Hospital (Shanghai East Hospital) - 3240

Shanghai, 200120, China

COMPLETED

Hubei Cancer Hospital - 3237

Wuhan, 430079, China

COMPLETED

Städt. Klinikum München GmbH - 2204

Bogenhausen, 81925, Germany

RECRUITING

Kliniken Essen-Mitte - 2206

Essen, 45136, Germany

RECRUITING

Klinikum Esslingen GmbH - 2201

Esslingen am Neckar, 73730, Germany

RECRUITING

Lungenfachklinik Immenhausen - 2202

Immenhausen, 34376, Germany

RECRUITING

Klinikverbund Allgaü - Klinikum Kempten - 2205

Immenstädt, 87509, Germany

RECRUITING

Asklepios Fachkliniken Muenchen-Gauting - 2203

Muenchen-Gauting, 82131, Germany

RECRUITING

Clinica Oncologica Ospedali Riuniti Ancona - 2311

Ancona, 60126, Italy

RECRUITING

IRCCS Istituto Tumori Giovanni Paolo II - 2306

Bari, 70124, Italy

RECRUITING

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII - 2310

Bergamo, 24126, Italy

RECRUITING

Humanitas Istituto Clinico Catanese - 2312

Catania, 95045, Italy

RECRUITING

Ospedale San Raffaele - 2307

Milan, 20132, Italy

RECRUITING

Fondazione IRCCS Instituto Tumori Di Milano - 2305

Milan, 20133, Italy

NOT YET RECRUITING

Ospedale San Gerardo di Monza - 2302

Monza, 20900, Italy

RECRUITING

Azienda Ospedaliera Universitaria "Federico II" - 2304

Naples, 80131, Italy

RECRUITING

AOU Policlinico Giaccone, Università di Palermo - 2309

Palermo, 90129, Italy

RECRUITING

Universita degli Studi di Perugia - Ospedale Santa Maria della Misericordia - 2308

Perugia, 06132, Italy

RECRUITING

Universita Campus Bio-medico Di Roma (UCBM) - Policlinico Universitario - 2303

Roma, 00128, Italy

RECRUITING

Antoni van Leeuwenhoek - 2703

Amsterdam, 1066 CV, Netherlands

RECRUITING

Rijnstate Ziekenhuis - 2701

Arnhem, 6815, Netherlands

RECRUITING

ETZ Elisabeth - 2704

Tilburg, 5022 GC, Netherlands

RECRUITING

Chungbuk National University Hospital - 3101

Cheongju-si, 28644, South Korea

RECRUITING

Keimyung University Dongsan Hospital - 3102

Daegu, 42601, South Korea

RECRUITING

National Cancer Center - 3107

Goyang-si, 10408, South Korea

RECRUITING

Severance Hospital, Yonsei University Health System - 3104

Seoul, 03722, South Korea

RECRUITING

Asan Medical Centre - 3103

Seoul, 05505, South Korea

RECRUITING

Korea University Guro Hospital - 3106

Seoul, 08308, South Korea

RECRUITING

The Catholic University of Korea, St Vincent's Hospital - 3105

Suwon, 16247, South Korea

RECRUITING

Hospital General Universitario de Elche - 2401

Elche, 03203, Spain

RECRUITING

Hospital Universitario Lucus Augusti - 2405

Lugo, 27003, Spain

RECRUITING

Hospital General Universitario Gregorio Marañon - 2404

Madrid, 28007, Spain

RECRUITING

Hospital Regional Universitario de Malaga - 2403

Málaga, 29010, Spain

RECRUITING

Hospital General Universitario de Valencia - 2406

Valencia, 46014, Spain

RECRUITING

Fundacion Instituto Valenciano De Oncologia (IVO) - 2402

Valencia, 56009, Spain

RECRUITING

Adana Sehir Hastanesi - 2602

Adana, Turkey (Türkiye)

RECRUITING

Baskent University Adana - 2601

Adana, Turkey (Türkiye)

RECRUITING

Hacettepe Universitesi - 2609

Ankara, 06230, Turkey (Türkiye)

RECRUITING

Ankara Bilkent Sehir Hastanesi - 2610

Ankara, 06800, Turkey (Türkiye)

RECRUITING

Akdeniz University Medical Hospital - 2606

Antalya, Turkey (Türkiye)

RECRUITING

Trakya University Faculty of Medicine Edirne - 2608

Edirne, Turkey (Türkiye)

RECRUITING

Istanbul Üniversitesi Onkoloji Enstitüsü - 2613

Fatih, 34093, Turkey (Türkiye)

RECRUITING

Koc Universitesi - 2611

Istanbul, 34010, Turkey (Türkiye)

RECRUITING

Göztepe Prof Dr. Suleyman Yalcin City Hospital - 2605

Istanbul, Turkey (Türkiye)

RECRUITING

Istanbul Bakirkoy Sadi Konuk - 2604

Istanbul, Turkey (Türkiye)

RECRUITING

Medipol University Medical Faculty Hospital - 2603

Istanbul, Turkey (Türkiye)

RECRUITING

Izmir Ekonomi Universitesi Medical Point Hastanesi - 2607

Izmir, Turkey (Türkiye)

RECRUITING

University Hospital Birmingham (UHB) / Queen Elizabeth Hospital Birmingham - 2801

Birmingham, England, B15 2TG, United Kingdom

RECRUITING

Cambridge University Hospitals - 2804

Cambridge, England, CB2 0QQ, United Kingdom

RECRUITING

Royal Devon University Healthcare NHS - 2808

Exeter, England, EX25DW, United Kingdom

NOT YET RECRUITING

University Hospital Leicester - 2806

Leicester, England, LE1 5WW, United Kingdom

RECRUITING

Barts Health NHS Trust (St. Bartholomew's Hospital) - 2803

London, England, EC1A 7BE, United Kingdom

RECRUITING

South Tees Hospitals - 2807

Middlesbrough, England, TS4 3BW, United Kingdom

RECRUITING

Torbay and South Devon NHS Foundation Trust - 2805

Torquay, England, TQ2 7AA, United Kingdom

RECRUITING

The Christie NHS Foundation Trust - 2802

Manchester, London, M20 4BX, United Kingdom

RECRUITING

Edinburgh Cancer Centre - 2809

Edinburgh, Scotland, EH54 6PP, United Kingdom

RECRUITING

University College London Hospital - 2811

London, NW1 2PG, United Kingdom

RECRUITING

Related Publications (3)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 cancer: stage 1 of the randomized phase 3 PRESERVE-003 trial. Nat Med. 2026 Mar 27. doi: 10.1038/s41591-026-04323-8. Online ahead of print.

  PMID: 41896648 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pan Zheng, MD, PhD

CONTACT

2027516823; pzheng@oncoc4.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: December 26, 2022
• First Posted: January 4, 2023
• Study Start: June 28, 2023
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6); DE (6); GB (10); CA (3); US (46); BE (4); IT (11); NL (3); KR (7); CN (40); TU (12); AU (4)