Clinical trial NCT05671510: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Non Small Cell Lung Cancer
Lead sponsor: OncoC4, Inc.
Sponsor class: INDUSTRY
Collaborators: name: BioNTech SE
First posted: 2023-01-04
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, open-label, active controlled, multi-center Phase 3 study.
Primary purpose: TREATMENT

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.

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 squamous 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 36 months
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: 36 months
measure: Progression-free survival (PFS)
timeFrame: 36 months
measure: Treatment emergent adverse events, treatment related adverse events and immune related adverse events.
timeFrame: 36 months
Other outcomes:
Locations:
city: Dothan
country: United States
facility: XCancer/Dothan Hematology & Oncology - 1114
state: Alabama
city: Russellville
country: United States
facility: Genesis Cancer and Blood Institute - 1123
state: Arkansas
city: Cerritos
country: United States
facility: The Oncology Institute (TOI) Clinical Research - 1109
state: California
city: Redlands
country: United States
facility: Emad Ibrahim MD Inc. - 1147
state: California
city: Sacramento
country: United States
facility: UC Davis Comprehensive Cancer Center - 1103
state: California
city: Walnut Creek
country: United States
facility: Bass Medical Group - 1155
state: California
city: Norwalk
country: United States
facility: Nuvance Health - 1118
state: Connecticut
city: Margate
country: United States
facility: D&H Cancer Research Center LLC - 1153
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center PL - 1102
state: Florida
city: Orlando
country: United States
facility: AdventHealth Cancer Institute - 1105
state: Florida
city: Orlando
country: United States
facility: Orlando Health - 1130
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists -South - 1126
state: Florida
city: The Villages
country: United States
facility: Florida Cancer Specialists -North - 1125
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists -East - 1124
state: Florida
city: Skokie
country: United States
facility: Orchard Healthcare Research, Inc. - 1116
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic - The Cancer Center - 1110
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology - 1133
state: Indiana
city: Newburgh
country: United States
facility: Deaconess Chancellor Center for Oncology - 1131
state: Indiana
city: Merriam
country: United States
facility: Alliance for Multispecialty Research, LLC - 1144
state: Kansas
city: Topeka
country: United States
facility: Cotton O'Neil Clinical Research Center - 1151
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky - Markey Cancer Center - 1112
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute - 1108
state: Kentucky
city: Baton Rouge
country: United States
facility: Hematology Oncology Clinics - Baton Rouge - 1142
state: Louisiana
city: Saint Louis Park
country: United States
facility: HealthPartners Institute, Cancer Research Center - 1143
state: Minnesota
city: Jefferson City
country: United States
facility: Jefferson City Medical Group - 1145
state: Missouri
city: Lincoln
country: United States
facility: NHO-Revive Research Institute, LLC - 1152
state: Nebraska
city: East Brunswick
country: United States
facility: Astera Cancer Care - 1128
state: New Jersey
city: Asheville
country: United States
facility: Messino Cancer Centers - 1121
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Center - 1107
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University James Cancer Center - 1104
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital - 1115
state: Ohio
city: Massillon
country: United States
facility: Tri County Hematology & Oncology Associates, Inc - 1156
state: Ohio
city: Eugene
country: United States
facility: Oncology Associates of Oregon - 1138
state: Oregon
city: Gettysburg
country: United States
facility: Pennsylvania Cancer Specialists Research Institute - 1101
state: Pennsylvania
city: Sayre
country: United States
facility: Donald Guthrie Foundation - 1135
state: Pennsylvania
city: York
country: United States
facility: Cancer Care Associates of York, Inc. - 1113
state: Pennsylvania
city: Knoxville
country: United States
facility: University of Tennessee Medical Center - 1146
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Tennessee Oncology at Nashville - 1119
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology -Dallas - 1127
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center (USOR) - 1140
state: Texas
city: Denison
country: United States
facility: Texas Oncology - Denison - 1139
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth Cancer Center - 1141
state: Texas
city: Houston
country: United States
facility: Oncology Consultants, P.A. - 1120
state: Texas
city: McAllen
country: United States
facility: Texas Oncology - McAllen - 1132
state: Texas
city: Plano
country: United States
facility: Texas Oncology - Plano West - 1137
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology -San Antonio - 1122
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Northeast Texas - Tyler - 1134
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology - Virginia - 1129
state: Virginia
city: Henrico
country: United States
facility: Virginia Cancer Institute - 1149
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates - 1136
state: Virginia
city: Spokane
country: United States
facility: MultiCare Institute for Research and Innovation - Tacoma - 1148
state: Washington
city: Bankstown
country: Australia
facility: Bankstown Hospital - 3305
state: New South Wales
city: New Lambton Heights
country: Australia
facility: Newcastle Private Hospital - 3302
state: New South Wales
city: Newstead
country: Australia
facility: Mater - 3301
state: Queensland
city: Adelaide
country: Australia
facility: Cancer Research SA - 3303
state: South Australia
city: Gent
country: Belgium
facility: AZ Maria Middelares - 2104
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis (Jessa Hospital) - Campus Salvator - 2102
city: Liège
country: Belgium
facility: C. H. R. de la Citadelle - 2103
city: Sint-Niklaas
country: Belgium
facility: Vitaz - Sint-niklaas Moerland - 2101
city: Kelowna
country: Canada
facility: BC Cancer Centre - Kelowna - 1203
state: British Columbia
city: Regina
country: Canada
facility: Saskatchewan Cancer Agency - Regina - 1201
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatchewan Cancer Agency - Saskatoon Cancer Centre - 1202
state: Saskatchewan
city: Québec
country: Canada
facility: Santa Cabrini Hospital - 1204
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University - 3221
state: Anhui
city: Hefei
country: China
facility: Anhui Medical University - The Second Hospital - 3222
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer Hospital - 3205
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences - 3211
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital - 3225
state: Fujian
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University - 3210
state: Fujian
city: Dongguan
country: China
facility: Dongguan People's Hospital - 3206
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital - 3201
state: Guangdong
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University - 3203
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangdong Pharmaceutical University - 3215
state: Guangdong
city: Nanning
country: China
facility: The People's Hospital of Guangxi Zhuang Autonomous Region - 3228
state: Guangxi
city: Haikou
country: China
facility: Hainan General Hospital - 3202
state: Hainan
city: Zhengzhou
country: China
facility: Affiliated Hospital of Hebei University - 3214
state: Hebei
city: Harbin
country: China
facility: The Affiliated Tumor Hospital of Harbin Medical University - 3232
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital - 3226
state: Henan
city: Zhengzhou
country: China
facility: The First Affliated Hospital of Zhengzhou University - 3207
state: Henan
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University - 3216
state: Hubei
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College - 3212
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital, Central South University - 3223
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital - 3209
state: Hunan
city: Suzhou
country: China
facility: The Second Affiliated Hospital of Soochow University - 3217
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Medical University - The Affiliated Hospital - 3234
state: Jiangsu
city: Nanchang
country: China
facility: The Second Affiliated Hospital of Nanchang University - 3224
state: Jiangxi
city: Jinan
country: China
facility: Jinan Central Hospital - 3230
state: Shandong
city: Taiyuan
country: China
facility: Shanxi Bethune Hospital - 3233
state: Shanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University - 3218
state: Shanxi
city: Chengdu
country: China
facility: Chengdu Seventh People's Hospital - 3229
state: Sichuan
city: Chengdu
country: China
facility: Sichuan Cancer Hospital - 3227
state: Sichuan
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital - 3213
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital - 3208
state: Tianjin
city: Kunming
country: China
facility: Yunnan Cancer Hospital - 3231
state: Yunnan
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine - 3219
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine - 3220
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital - 3204
state: Zhejiang
city: Beijing
country: China
facility: China-Japan Friendship Hospital - 3236
city: Chengdu
country: China
facility: West China Hospital, Sichuan University - 3238
city: Jiangse
country: China
facility: Nanjing Medical University (NMU) - Nanjing First Hospital - 3239
city: Shandong
country: China
facility: Weifang Second People's Hospital - 3235
city: Shanghai
country: China
facility: Tongji University - Shanghai Oriental Hospital (Shanghai East Hospital) - 3240
city: Wuhan
country: China
facility: Hubei Cancer Hospital - 3237
city: Billancourt
country: France
facility: Hôpital Ambroise Paré - 2501
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil - 2502
city: Limoges
country: France
facility: CHU Limoges - Hospital du Cluzeau - 2503
city: Bogenhausen
country: Germany
facility: Städt. Klinikum München GmbH - 2204
city: Essen
country: Germany
facility: Kliniken Essen-Mitte - 2206
city: Esslingen am Neckar
country: Germany
facility: Klinikum Esslingen GmbH - 2201
city: Immenhausen
country: Germany
facility: Lungenfachklinik Immenhausen - 2202
city: Immenstädt
country: Germany
facility: Klinikverbund Allgaü - Klinikum Kempten - 2205
city: Muenchen-Gauting
country: Germany
facility: Asklepios Fachkliniken Muenchen-Gauting - 2203
city: Ancona
country: Italy
facility: Clinica Oncologica Ospedali Riuniti Ancona - 2311
city: Bari
country: Italy
facility: IRCCS Istituto Tumori Giovanni Paolo II - 2306
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII - 2310
city: Messina
country: Italy
facility: Azienda Ospedaliera Papardo - 2301
city: Milano
country: Italy
facility: Ospedale San Raffaele - 2307
city: Milano
country: Italy
facility: Fondazione IRCCS Instituto Tumori Di Milano - 2305
city: Monza
country: Italy
facility: Ospedale San Gerardo di Monza - 2302
city: Naples
country: Italy
facility: Azienda Ospedaliera Universitaria "Federico II" - 2304
city: Palermo
country: Italy
facility: AOU Policlinico Giaccone, Università di Palermo - 2309
city: Perugia
country: Italy
facility: Universita degli Studi di Perugia - Ospedale Santa Maria della Misericordia - 2308
city: Roma
country: Italy
facility: Universita Campus Bio-medico Di Roma (UCBM) - Policlinico Universitario - 2303
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital - 3101
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital - 3102
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center - 3107
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System - 3104
city: Seoul
country: Korea, Republic of
facility: Asan Medical Centre - 3103
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital - 3106
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea, St Vincent's Hospital - 3105
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek - 2703
city: Arnhem
country: Netherlands
facility: Rijnstate Ziekenhuis - 2701
city: Herzogenbusch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis - 2702
city: Tilburg
country: Netherlands
facility: ETZ Elisabeth - 2704
city: Elche
country: Spain
facility: Hospital General Universitario de Elche - 2401
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti - 2405
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon - 2404
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga - 2403
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia - 2406
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano De Oncologia (IVO) - 2402
city: Adana
country: Turkey
facility: Adana Sehir Hastanesi - 2602
city: Adana
country: Turkey
facility: Baskent University Adana - 2601
city: Ankara
country: Turkey
facility: Hacettepe Universitesi - 2609
city: Ankara
country: Turkey
facility: Ankara Bilkent Sehir Hastanesi - 2610
city: Antalya
country: Turkey
facility: Akdeniz University Medical Hospital - 2606
city: Bornova
country: Turkey
facility: Ege Universitesi Hastanesi - 2612
city: Edirne
country: Turkey
facility: Trakya University Faculty of Medicine Edirne - 2608
city: Fatih
country: Turkey
facility: Istanbul Üniversitesi Onkoloji Enstitüsü - 2613
city: Istanbul
country: Turkey
facility: Koc Universitesi - 2611
city: Istanbul
country: Turkey
facility: Göztepe Prof Dr. Suleyman Yalcin City Hospital - 2605
city: Istanbul
country: Turkey
facility: Istanbul Bakirkoy Sadi Konuk - 2604
city: Istanbul
country: Turkey
facility: Medipol University Medical Faculty Hospital - 2603
city: İzmir
country: Turkey
facility: Izmir Ekonomi Universitesi Medical Point Hastanesi - 2607
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham (UHB) / Queen Elizabeth Hospital Birmingham - 2801
state: England
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals - 2804
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon University Healthcare NHS - 2808
state: England
city: Leicester
country: United Kingdom
facility: University Hospital Leicester - 2806
state: England
city: London
country: United Kingdom
facility: The Christie NHS Foundation Trust - 2803
state: England
city: Manchester
country: United Kingdom
facility: Barts Health NHS Trust (St. Bartholomew's Hospital) - 2802
state: England
city: Middlesbrough
country: United Kingdom
facility: South Tees Hospitals - 2807
state: England
city: Southampton
country: United Kingdom
facility: University Hospital Southampton - 2810
state: England
city: Torquay
country: United Kingdom
facility: Torbay Hospital - Horizon Centre - 2805
state: England
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre - 2809
state: Scotland
Study officials:
affiliation: Advent Health System
name: Mark Socinski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: Tianhong Li, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio State University
name: Kai He, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.