The investigators hypothesize that the addition of ramucirumab and N-803 will augment the clinical activity of atezolizumab, and in order to evaluate the exact mechanism of action of the combination, the investigators propose a comprehensive analysis of paired peripheral blood samples collected during this study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Will be supplied by Lilly Oncology, free of charge to the participant
Atezolizumab will be commercially available.
Will be supplied free of charge to the participants by ImmunityBio
Objective response rate (ORR)
* ORR is defined as the proportion of participants achieving complete response or partial response measured according to RECIST 1.1 * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Through completion of treatment (estimated to be 6 months)
Number of study treatment related adverse events as measured by NCI-CTCAE version 5.0
Time frame: From start of treatment through 30 days after completion of treatment (estimated to be 7 months)
Overall survival (OS)
-Defined as the duration of time from the start date of study treatment to death from any cause. Patients who are alive by the data cutoff date will be censored at the last follow up date.
Time frame: Through completion of follow-up (estimated to be 30 months)
Progression-free survival (PFS)
* PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. * Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase.
Time frame: Through completion of follow-up (estimated to be 30 months)
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Immune best overall response (iBOR)
* Defined as the best time point response recorded from the start of the study treatment until the end of treatment, taking into account any requirement for confirmation. * iBOR will be measured by iRECIST criteria
Time frame: Through completion of treatment (estimated to be 6 months)
Immune progression-free survival (iPFS)
* Defined by the first date at which progression criteria are met (i.e., the date of immune unconfirmed progression (iUPD) provided that immune confirmed progression (iCPD) is confirmed at the next assessment). If iUPD occurs, but later that patient develops immune stable disease (iSD), immune partial response (iPR), or immune complete response (iCR), then this initial iUPD date is not the date of PD. If progression is not confirmed and there is no subsequent iSD, iPR, or iCR, then the iUPD date should still be used in the following scenarios: if the patient stops protocol treatment because they were not judged to be clinically stable, or no further response assessments are done (because of patient refusal, protocol noncompliance, or patient death); the next time point response are all iUPD, and iCPD never occurs; or the patient dies from their cancer. * Progression will be measured per iRECIST criteria
Time frame: Through completion of follow-up (estimated to be 30 months)
Clinical benefit rate (CBR)
* Defined as the percentage of participants who have achieved complete response, partial response, or stable disease measured according to RECIST 1.1 * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Through completion of treatment (estimated to be 6 months)
Number of discontinuations due to treatment-related adverse events
Time frame: From start of treatment through completion of treatment (estimated to be 6 months)