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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04140526




Registration number
NCT04140526
Ethics application status
Date submitted
24/10/2019
Date registered
28/10/2019
Date last updated
13/05/2024

Titles & IDs
Public title
Safety, PK and Efficacy of ONC-392 in Monotherapy and in Combination of Anti-PD-1 in Advanced Solid Tumors and NSCLC
Scientific title
Safety, Pharmacokinetics (PK), and Efficacy of ONC-392 as a Single Agent and in Combination With Pembrolizumab in Advanced Solid Tumors and NSCLC: An Open Label Phase IA/IB Study. Preserve CTLA4 Checkpoint Function (PRESERVE-001)
Secondary ID [1] 0 0
4R44CA250824-02
Secondary ID [2] 0 0
ONC-392-001
Universal Trial Number (UTN)
Trial acronym
PRESERVE-001
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non Small Cell Lung Cancer 0 0
Advanced Solid Tumor 0 0
Metastatic Melanoma 0 0
Metastatic Head and Neck Carcinoma 0 0
Metastatic Renal Cell Carcinoma 0 0
Metastatic Colorectal Cancer 0 0
Sarcomas 0 0
Metastatic Prostate Cancer 0 0
Ovarian Cancer 0 0
Small Cell Lung Cancer 0 0
Metastatic Breast Cancer 0 0
Pancreas Cancer 0 0
Gastric Cancer 0 0
Esophageal Cancer 0 0
Gastroesophageal Junction Adenocarcinoma 0 0
Cervical Cancer 0 0
Adenoid Cystic Carcinoma 0 0
Salivary Gland Cancer 0 0
Urothelial Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell
Cancer 0 0 0 0
Head and neck
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Pancreatic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ONC-392
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Docetaxel

Experimental: ONC-392 Treatment as single agent - The Part A study will test ONC-392 intravenous (IV) infusion up to five predefined dose levels from 0.1 mg/kg to 10 mg/kg ONC-392 as monotherapy every 21 days (Q3W). The Part A study will determine the maximal tolerable dose (MTD) and the recommended Phase 2 dose in monotherapy (RP2D-M).
In Part C, Arms A-C, I-N monotherapy expansion cohorts will further assess the safety and efficacy of ONC-392 in different dose levels as monotherapy in pancreatic cancer, triple negative breast cancer, non small cell lung cancer with driver mutations, PD-1 resistant non small cell lung cancer, PD-1 resistant melanoma, head and neck cancer, ovarian cancer, renal cell carcinoma and other solid tumors.
Part D is a Phase II study on recurrent and/or metastatic adenoid cystic carcinoma.

Experimental: ONC-392 in combination with pembrolizumab - The Part B1 study will test ONC-392 intravenous (IV) infusion, Q3W, in combination with fixed dose of pembrolizumab. The dose for pembrolizumab will be fixed at 200mg/cycle dosed every 21 days (Q3W).
The Part B1 will start at one level below RP2D-M dose for ONC-392 and 200mg of pembrolizumab. When 2 DLTs occur before 6 patients are enrolled, the ONC-392 dose will be decreased to the next dose level until = 1/6 patients treated at that dose develops a DLT. This dose level will be designated RP2D-C.
In Part C, the expansion cohorts Arm D to G will assess the safety and efficacy of ONC-392 in different dose levels and Pembrolizumab combination therapy in non small cell lung cancer, and metastatic melanoma.

Experimental: ONC-392 and docetaxel - Part E Arm O will test ONC-392 in combination with docetaxel, IV infusion, Q3W, in PD-1 resistant NSCLC patients.


Treatment: Drugs: ONC-392
ONC-392 will be given by intravenous infusion, once every 21 days (Q3W). In Part C Arm M and in Part D, ONC-392 will be given Q4W.

Treatment: Drugs: Pembrolizumab
Pembrolizumab will be given intravenous (IV) infusion at 200 mg/cycle, once every 21 days (Q3W).

Treatment: Drugs: Docetaxel
Docetaxel will be given intravenous (IV) infusion at 75 mg/m2, once every 21 days (Q3W).
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Dose limiting toxicity (DLT) in monotherapy
Timepoint [1] 0 0
21 days
Primary outcome [2] 0 0
Maximal tolerable dose (MTD) in monotherapy
Timepoint [2] 0 0
21 days
Primary outcome [3] 0 0
Recommended Phase II Dose (RP2D)
Timepoint [3] 0 0
21 days
Primary outcome [4] 0 0
Rate of treatment related adverse events (TRAE) according to CTCAE v5.0
Timepoint [4] 0 0
One year
Secondary outcome [1] 0 0
The serum half life of the study drug, ONC-392, in monotherapy.
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
The serum half life of the study drug, ONC-392, in combination therapy with Pembrolizumab.
Timepoint [2] 0 0
12 weeks
Secondary outcome [3] 0 0
Objective Response Rate (ORR)
Timepoint [3] 0 0
1 year
Secondary outcome [4] 0 0
Progression Free Survival (PFS)
Timepoint [4] 0 0
1 year
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
1 year

Eligibility
Key inclusion criteria
1. . Patients must have a histological or cytological diagnosis of NSCLC or any other
type of carcinoma or sarcomas, progressive metastatic disease, or progressive locally
advanced disease not amenable to local therapy.

1. In the Part A Phase I dose escalation study of ONC-392 monotherapy, patients with
advanced/metastatic solid tumors of any histology are eligible for participation.

Please note: tumor types of primary interest in this study are malignant
melanoma, renal cell carcinoma, hepatocellular carcinoma, non-small cell lung
cancer, head and neck carcinoma, gastric carcinoma, ovarian carcinoma, colorectal
cancer, any type of sarcoma.

2. In Part B dose finding of the ONC-392 plus pembrolizumab combination, patients
with advanced/metastatic solid tumors of any histology that Pembrolizumab has
been approval as standard of care are eligible for participation.

3. In Part C, patients with pancreatic cancer, triple negative breast cancer, non
small cell lung cancer, melanoma, Head and Neck cancer, ovarian cancer, and other
solid tumors are eligible.

4. In Part D, patients with recurrent and/or metastatic adenoid cystic carcinoma
with disease progression within 12 months are eligible.

5. Patients must have RECIST V1.1 Measurable disease:

2. Patient is male or female and >18 years of age on day of signing informed consent.

3. Patient must have a performance status of 0 or 1 on the ECOG Performance Scale

4. Patient must have adequate organ function as indicated by the following laboratory
values:

Hematological: Absolute neutrophil count (ANC) =1,500 /mcL; Plateletsa =100,000 / mcL;
Hemoglobin =9 g/dL or =5.6 mmol/L- without qualifications; Renal: Serum creatinine
=1.5 X upper limit of normal (ULN); Hepatic: Serum total bilirubin =1.5 X ULN; OR
Direct bilirubin = ULN for patients with total bilirubin levels >1.5 ULN; AST (SGOT)
and ALT (SGPT) =2.5 X ULN, OR =5 X ULN for patients with active liver metastases
Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) =1.5 X ULN
Activated Partial Thromboplastin Time (aPTT) =1.5 X ULN

5. Patient has voluntarily agreed to participate by giving written informed consent.

6. Female patient of childbearing potential has a negative urine or serum pregnancy test.

7. Female and Male patients must agree to use adequate methods of contraception starting
with the first dose of study drug through 90 days after the last dose of study
therapy.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
A patient meeting any of the following criteria is not eligible to participate in this
study:

1. Patients who have not recovered to CTCAE = 1 from the AE due to cancer therapeutics.
The washout period for cancer therapeutic drugs (such as chemotherapy, radioactive, or
targeted therapy) is 21 days, and for antibody drug 28 days.

2. Patients who are currently enrolled in a clinical trial of an investigational agent or
device.

3. Patients who are on chronic systemic steroid therapy at doses >10 mg/day

4. Patients who have active symptomatic brain metastasis or leptomeningeal metastasis.

5. Patients who have an active infection requiring systemic IV therapy within 14 days of
prior to administration of ONC-392 or combined ONC-392 and Pembrolizumab.

6. Patients who have a history or current evidence of any condition, therapy, or
laboratory abnormality that might confound the results of the study, interfere with
the patient's participation for the full duration of the study, or is not in the best
interest of the patient to participate, in the opinion of the treating Investigator.

7. Patients with known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

8. Patients who are pregnant or breastfeeding.

9. For the Part B and Part C Arm D to G, the patients that are deemed to be not suitable
for Pembrolizumab.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/09/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2027
Actual
Sample size
Target
733
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
Newcastle Private Hospital - New Lambton Heights
Recruitment hospital [2] 0 0
Tasman Oncology Research - Southport
Recruitment hospital [3] 0 0
Cancer Research SA - Adelaide
Recruitment hospital [4] 0 0
Southern Oncology Clinical Research Unit - Bedford Park
Recruitment postcode(s) [1] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [2] 0 0
4120 - Southport
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
5042 - Bedford Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
South Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
OncoC4, Inc.
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a First-in-Human Phase IA/IB/II open label dose escalation study of intravenous (IV)
administration of ONC-392, a humanized anti-CTLA4 IgG1 monoclonal antibody, as single agent
and in combination with pembrolizumab in participants with advanced or metastatic solid
tumors and non-small cell lung cancers.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04140526
Trial related presentations / 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.
Du X, Tang F, Liu M, Su J, Zhang Y, Wu W, Devenport M, Lazarski CA, Zhang P, Wang X, Ye P, Wang C, Hwang E, Zhu T, Xu T, Zheng P, Liu Y. A reappraisal of CTLA-4 checkpoint blockade in cancer immunotherapy. Cell Res. 2018 Apr;28(4):416-432. doi: 10.1038/s41422-018-0011-0. Epub 2018 Feb 22.
Du X, Liu M, Su J, Zhang P, Tang F, Ye P, Devenport M, Wang X, Zhang Y, Liu Y, Zheng P. Uncoupling therapeutic from immunotherapy-related adverse effects for safer and effective anti-CTLA-4 antibodies in CTLA4 humanized mice. Cell Res. 2018 Apr;28(4):433-447. doi: 10.1038/s41422-018-0012-z. Epub 2018 Feb 20.
May KF Jr, Roychowdhury S, Bhatt D, Kocak E, Bai XF, Liu JQ, Ferketich AK, Martin EW Jr, Caligiuri MA, Zheng P, Liu Y. Anti-human CTLA-4 monoclonal antibody promotes T-cell expansion and immunity in a hu-PBL-SCID model: a new method for preclinical screening of costimulatory monoclonal antibodies. Blood. 2005 Feb 1;105(3):1114-20. doi: 10.1182/blood-2004-07-2561. Epub 2004 Oct 14.
Lute KD, May KF Jr, Lu P, Zhang H, Kocak E, Mosinger B, Wolford C, Phillips G, Caligiuri MA, Zheng P, Liu Y. Human CTLA4 knock-in mice unravel the quantitative link between tumor immunity and autoimmunity induced by anti-CTLA-4 antibodies. Blood. 2005 Nov 1;106(9):3127-33. doi: 10.1182/blood-2005-06-2298. Epub 2005 Jul 21.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Tianhong Li, MD
Address 0 0
University of California, Davis
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Pan Zheng, MD, PhD
Address 0 0
Country 0 0
Phone 0 0
202 751 6823
Fax 0 0
Email 0 0
pzheng@oncoc4.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04140526