This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with NSCLC who have progressed on or after treatment with PD-1/PD-L1 inhibitors.
Treatment will be administered in 2 phases, an induction and a maintenance phase, as described below. Subjects will continue induction treatment for up to 1 year. Treatment in the study will be discontinued if the subject experiences progressive disease (PD) or unacceptable toxicity (not correctable with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. Those who have a complete response (CR) in the induction phase will enter the maintenance phase of the study. Subjects may remain on the maintenance phase of the study for up to 1 year. Treatment will continue in the maintenance phase until the subject experiences PD or unacceptable toxicity (not correctable with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Fully human anti-PD-L1 IgG1 lambda monoclonal antibody
Recombinant human anti-vascular endothelial growth factor (VEGF) immunoglobulin (Ig) G1 monoclonal antibody
5'-deoxy-5-fluoro-N-\[(pentyloxy) carbonyl\]-cytidine
Incidence of treatment-emergent adverse events (AEs) and serious AEs (SAEs), graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.
Phase 1b primary endpoint (safety)
Time frame: 1 year
Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Phase 2 primary endpoint (ORR by RECIST)
Time frame: 1 year
ORR by Immune-related response criteria (irRC )
Phase 2 primary endpoint (ORR by irRC)
Time frame: 1 year
ORR by RECIST Version 1.1
Phase 1b secondary endpoint (ORR by RECIST)
Time frame: 1 year
ORR by irRC
Phase 1b secondary endpoint (ORR by irRC)
Time frame: 1 year
Progression-free survival (PFS) by RECIST Version 1.1
Phase 1b and 2 secondary endpoint (PFS by RECIST)
Time frame: 2 years
PFS by irRC
Phase 1b and 2 secondary endpoint (PFS by irRC)
Time frame: 2 years
Overall survival (OS): time from the date of first treatment to the date of death (any cause)
Phase 1b and 2 secondary endpoint (OS)
Time frame: 2 years
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(SP-4-2)-diamminedichloroplatinum(II)
2-\[bis(2-chloroethyl)amino\]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
5-fluoro-2,4 (1H,3H)-pyrimidinedione
7-alpha-\[9-(4,4,5,5,5-pentafluoropentylsulphinyl) nonyl\]estra-1,3,5-(10)- triene-3,17-beta-diol
Calcium N-\[p-\[\[\[(6RS)-2-amino-5- formyl-5,6,7,8-tetrahydro-4-hydroxy-6- pteridinyl\]methyl\]amino\]benzoyl\]-L-glutamate (1:1)
5β,20-Epoxy-1,2α,4,7β,10β,13α-hexahydroxytax-11- en-9-one 4,10-diacetate 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisoserine
Human anti-PD-1 IgG4 kappa monoclonal antibody
Omega-3-acid ethyl esters
cis-\[(1 R,2 R)-1,2-cyclohexanediamine-N,N'\] \[oxalato(2-)- O,O'\] platinum
(SRBT)
recombinant human super agonist interleukin-15 (IL-15) complex \[also known as IL15N72D:IL-15RαSu/IgG1 Fc complex\]
adenovirus serotype-5 \[Ad5\] \[E1-, E2b-\]-carcinoembryonic antigen \[CEA\] vaccine
Ad5 \[E1-, E2b-\]-human epidermal growth factor receptor 2 \[HER2\] vaccine
Ad5 \[E1-, E2b-\]-Brachyury vaccine
Ad5 \[E1-, E2b-\]-mucin 1 \[MUC1\] vaccine
Ras yeast vaccine
CEA yeast vaccine
Brachyury yeast vaccine
NK-92 \[CD16.158V, ER IL-2\], Suspension for Intravenous \[IV\] Infusion
Duration of response (DR): time from the date of first response (partial response (PR) or complete response (CR)) to the date of disease progression or death (any cause) whichever occurs first
Phase 1b and 2 secondary endpoint (DR)
Time frame: 2 years
Disease control rate (DCR): confirmed complete response, partial response, or stable disease lasting for at least 2 months
Phase 1b and 2 secondary endpoint (DCR)
Time frame: 2 months
Quality of life (QoL) by patient-reported outcome using the Functional Assessment of Cancer Therapy-Lung (FACT-L)
Phase 1b and 2 secondary endpoint (QoL)
Time frame: 2 years
Incidence of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs), graded using the NCI CTCAE Version 4.03
Phase 2 secondary endpoint (AEs)
Time frame: 2 years