This is a phase 1b/2 study to evaluate the safety and efficacy of metronomic combination therapy in subjects with TNBC who have progressed on or after previous SoC chemotherapy. Phase 2 will be based on Simon's two-stage optimal design.
Treatment will be administered in two 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 corrected 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 who experience ongoing stable disease (SD) or an ongoing partial response (PR) at 1 year may enter the maintenance phase at the Investigator's discretion. 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 corrected with dose reduction), withdraws consent, or if the Investigator feels it is no longer in the subject's best interest to continue treatment. The maximum time on study treatment, including both the induction and maintenance phases, is 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Chan Soon-Shiong Institute for Medicine
El Segundo, California, United States
Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)
Graded using the NCI CTCAE Version 4.03.
Time frame: Up to 2 years
Objective Response Rate by RECIST v1.1
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT) or magnetic resonance imaging (MRI) of target and non-target lesions in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Percent of subjects with confirmed complete Response (CR; disappearance of all target lesions) or partial response (PR; \>=30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum diameters.
Time frame: Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression. Up to 2.5 years
Objective Response Rate by irRC (Percent of Subjects With Confirmed Complete or Partial Overall Response)
Tumors will be assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase by computed tomography (CT) or magnetic resonance imaging (MRI) of target and non-target lesions in accordance with Response Evaluation Criteria in Solid Tumors (irRC) Version 1.1. Percent of subjects with confirmed complete Response or partial response by irRC.
Time frame: Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until confirmed disease progression. Up to 2.5 years.
Progression Free Survival by RECIST v1.1
PFS were defined as the time from the date of first treatment to the date of disease progression or death (any cause), whichever occured first. Subjects completing study follow-up or starting a new anticancer therapy prior to documented PD were censored in the PFS analysis at the last known date the subject was progression free prior to completing follow-up or initiating new therapy.
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Ad5 \[E1-, E2b-\]-Brachyury vaccine
Ad5 \[E1-, E2b-\]-MUC1
Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Ras proteins
Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant CEA proteins
Vaccine derived from recombinant Saccharomyces cerevisiae yeast expressing mutant Brachyury yeast proteins
NK-92 \[CD16.158V, ER IL-2\]
Recombinant human anti-PD-L1 IgG1 monoclonal antibody
Recombinant human anti-VEGF IgG1 monoclonal
5'-deoxy-5-fluoro-N-\[(pentyloxy) carbonyl\]-cytidine
cis-diamminedichloroplatinum(II)
2-\[bis(2-chloroethyl)amino\]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate
5-fluoro-2,4 (1H,3H)-pyrimidinedione
L-Glutamic acid, N-\[4-\[\[(2-amino-5-formyl-1,4,5,6,7,8-hexahydro-4-oxo-6-pteridinyl)methyl\]amino\]benzoyl\]-, calcium salt
Benzenepropanoic acid, β-(benzoylamino)-α-hydroxy-(2aR, 4S, 4aS, 6R, 9S, 11S, 12S, 12aR, 12bS)-6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a, 3, 4, 4a, 5, 6, 9, 10, 11, 12, 12a, 12b-dodecahydro-4,11-dihydroxy-4a, 8, 13, 13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca\[3,4\]benz\[1,2-b\]oxet-9-y1ester,(αR,βS)-(9CI) bound to albumin
Stereotactic Body Radiation Therapy
Time frame: Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first. Up to 2.5 years.
Progression Free Survival by irRC
PFS were defined as the time from the date of first treatment to the date of disease progression or death (any cause), whichever occured first. Subjects completing study follow-up or starting a new anticancer therapy prior to documented PD were censored in the PFS analysis at the last known date the subject was progression free prior to completing follow-up or initiating new therapy.
Time frame: Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first.
Duration of Response by RECIST Version 1.1
DOR were evaluated using Kaplan-Meier methods for those subjects with a confirmed response. DOR were defined as the time from the date of first response (PR or CR) to the date of disease progression or death (any cause) whichever occured first. Responding subjects completing study follow-up or starting a new anticancer therapy prior to documented PD were censored in DOR analysis at the last known date the subject was progression free prior to completing follow-up or initiating new therapy.
Time frame: Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first.
Disease Control Rate by RECIST Version 1.1
Disease control was defined as subjects with a confirmed Complete Response (CR), Partial Response (PR), or Stable Disease (SD) lasting for at least 2 months. Complete response (CR; disappearance of all target lesions) or partial response (PR; \>=30% decrease in the sum of the longest diameter of target lesions) or stable disease (SD; Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD)
Time frame: Tumors were assessed at screening, and tumor response will be assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression. Up to 2.5 years.
Duration of Response by irRC
DOR were evaluated using Kaplan-Meier methods for those subjects with a confirmed response. DOR were defined as the time from the date of first response (PR or CR) to the date of disease progression or death (any cause) whichever occured first. Responding subjects completing study follow-up or starting a new anticancer therapy prior to documented PD were censored in DOR analysis at the last known date the subject was progression free prior to completing follow-up or initiating new therapy.
Time frame: Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first.
Disease Control Rate by irRC
Disease control was defined as subjects with a confirmed Complete Response (irCR), Partial Response (irPR), or Stable Disease (irSD) lasting for at least 2 months. Complete response (irCR; disappearance of all index lesions) or partial response (irPR; \>=100% decrease in the sum of the longest diameter of index lesions with stable non-index lesions or \>=50% decrease in the sum of index lesions with absent/stable /progressed non-index lesions) or stable disease (irSD; Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD)
Time frame: Tumors were assessed at screening, and tumor response was assessed every 8 weeks during the induction phase, and every 12 weeks during the maintenance phase until disease progression or death (any cause) whichever occurred first. Up to 2.5 years.
Overall Survival
OS were evaluated using Kaplan-Meier methods. OS were defined as the time from the date of first treatment to the date of death (any cause). Subjects who are alive at the end of follow-up were censored in the OS analysis at the last known date alive.
Time frame: Evaluated from screening to death.
Quality of Life by Patient Reported Outcomes
Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) instrument on study
Time frame: Up to 2.5 years