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

Non Small Cell Lung Cancer Clinical Trial

— PRESERVE-003  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05671510
• Other study ID #: PRESERVE-003
• Status: Recruiting
• Phase: Phase 3
• Start date: June 28, 2023
• Est. completion date: June 30, 2027

Study information

• Verified date: May 2024
• Source: OncoC4, Inc.
• Contact: Pan Zheng, MD, PhD
• Phone: 2027516823
• Email: pzheng[@]oncoc4.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• 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.
• Docetaxel
Docetaxel will be administrated through IV infusion over 60 minutes, once every 21 days in 75mg/m2 dose.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
OncoC4, Inc.	BioNTech SE

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  China,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Spain,  Turkey,  United Kingdom, 

References & Publications (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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Objective response rate (ORR)	Objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) per RECIST 1.1	36 months
Secondary	Progression-free survival (PFS)	Progression-free survival (PFS) as assessed by Investigator per RECIST 1.1	36 months
Secondary	Treatment emergent adverse events, treatment related adverse events and immune related adverse events.	Incidence of TEAEs, TRAEs, irAEs will be calcuated. The AEs leading to treatment discontinuation will be recorded.	36 months