NSCLC
Conditions
Interventions
Stage I: Arm 1: ONC-392 6 mg/kg Q3W with two loading doses of 10 mg/kg Q3W:ONC-392 6 mg/kg Q3W with two loading doses of 10 mg/kg Q3W
Stage I:Arm 2: ONC-392 3 mg/kg Q3W:ONC-392 3 mg/kg Q3W
Stage I: Arm 3: Docetaxel 75 mg/m2 Q3W:Docetaxel 75 mg/m2 Q3W
Stage II:Arm 1 or 2: ONC-392 with the selected dosing regimen from Stage I:ONC-392 with the selected dosing regimen from Stage I
Stage II:Arm 3: Docetaxel 75 mg/m2 Q3W:Docetaxel 75 mg/m2 Q3W
Sponsors
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1?Adult, all genders, age >=18 years on the day of signing informed consent, voluntarily agree to participate by signing written informed consent. 2?Histologically- or cytologically- confirmed diagnosis of metastatic NSCLC, metastasis can be regional lymph nodes or distant organs. 3?Radiographic disease progression after treatment with the most recent line of treatment being 3a or 3b as follows: a. At least 12 weeks of standard doses of PD-1/PD-L1 inhibitor in combination with platinum-containing doublet chemotherapy;b. Prior treatment with at least 2 cycles of a platinum-containing doublet 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?Patient must have measurable disease lesions according to RECIST 1.1. 5?Patient must have a ECOG performance status 0 or 1. 6?Patient must have adequate organ function as indicated by the laboratory values. Absolute neutrophil count (ANC) >=1,500 /µL ;Platelets>= 100,000 / µL ; Hemoglobin>= 9 g/dL or>=5.6 mmol/L; Creatinine clearance as calculated per Cockcroft-Gault or MDRD formula >= 30 ml/min ; Serum total bilirubin =3 months. 8?Women of childbearing potential (WOCBP) and sexually active, must agree to use adequate and effective birth control starting from the screening visit (Visit 1) through 90 days after the last dose of study therapy. 9?.Male patients, if sexually active, must agree to use adequate and effective methods of contraception starting from the screening visit (Visit 1) through 90 days after the last dose of study therapy. 10?Patient agrees to grant study team the access to archival/ongoing diagnostic/ treatment tissue (recut slides or tumor biopsy) from biopsy or surgery as SOC procedure.
Exclusion criteria
Exclusion criteria: 1?Patients who have not recovered to NCI CTCAE Grade 1 or better from AEs due to cancer therapeutics except chemotherapy associated peripheral neuropathy (motor or sensory), or endocrine related AE, in which recovery to 10 mg/day prednisone or equivalent within 7 days of first day of study treatment. Topical steroid use is allowed. 4?Patients who have documented targetable mutations or genomic alterations in the following genes: EGFR, ROS1, MET, BRAF, RET, NTRK, ALK or HER2. Patients with mutation or genomic alterations in KRAS are not excluded. 5?Patients who have active or symptomatic brain metastases or evidence of progression within 4 weeks prior to study drug dosing. Palliative radiation or radiosurgery for brain metastases within 14 days from first day of study treatment or patients cannot achieve neurologically stable without > 10 mg daily prednisone or equivalent treatment. Patients with treated, stable brain metastases or with untreated asymptomatic brain metastases (<1 cm and without significant edema) are allowed to enroll. 6?Patients who have active GI disease, including peptic ulcer disease, pancreatitis, diverticulitis, or inflammatory bowel disease. Or patients who have abdominal fistula, bowel obstruction, GI perforation, or intra-abdominal abscess within 6 months before initiation of study treatment. 7?Patient who has any evidence of current interstitial lung disease (ILD) or pneumonitis, or a prior history of ILD or non-infectious pneumonitis that was associated with target therapy or anti-PD-1/PD-L1 based therapy and required high dose steroid. 8?Patients have active infections requiring systemic IV antibiotics within 14 days, or oral antibiotics within 7 days, from first day of study treatment. Regular treatment of urinary tract infection (UTI), upper respiratory infection (URI) and/or topical treatment are allowed. 9?Patients who had prior history of cardiovascular events, i.e., stroke, myocardial infarction, symptomatic pulmonary embolism, or other symptomatic ischemic event, within 6 months prior to initiation of study treatment; or history of myocarditis or congestive heart failure within 3 months prior to initiation of study treatment. 10?Patients who had history of severe hypersensitivity reactions to docetaxel or to drugs formulated with polysorbate 80. 11?Patients who have autoimmune diseases that require immunosuppressive medications; 12?Patients who had major surgical procedure, other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipate a major surgical procedure during the study. Palliative radiation therapy is allowed prior to and during study drug administration as long as there are no acute toxicities. 13?Patients who, in the opinion of the Investigator, have a history or current evidence of any medical or psychiatric condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| overall survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate;TEAEs;Population PK of ONC-392;ADA and its effect on ONC-392 PK, efficacy, and safety;Progression-free survival;Disease control rate;BOR;TRAEs;irAE;Aes;Exposure-response relationship for efficacy and safety; | — |
Countries
China
Contacts
Public ContactHuajun Chen
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Outcome results
None listed