Multicentric, prospective, multi-indication, single-treatment arm, open-label phase II trial assessing the efficacy of MEDI5752
Multicentric, prospective, multi-indication, single-treatment arm, open-label phase II trial assessing the efficacy of MEDI5752. Patients with mature tertiary lymphoid structures advanced solid tumors will be included in two independent cohorts: * Cohort A: patients with TLS+ IO-naïve solid tumor (miscellaneous) * Cohort B: patients with TLS+ PD1/PDL1-experienced solid tumor (miscellaneous) Each cohort will rely on a two-stage three-outcome design as described in Sargent et al.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
102
A treatment cycle consists of 3 weeks. MEDI5752 will be administered by intravenous infusion at a fixed dose on Day 1 of each cycle
Institut Bergonie
Bordeaux, France
Assessment of the antitumor activity of MEDI5752 (independently for eah cohort)
Antitumor activity will be assessed in terms of objective response rate within 24 weeks based on RECIST v1.1, independently for each cohort, and based on centralized radiological review. Objective response under treatment is defined as patients with confirmed complete response or confirmed partial response, as per RECIST v1.1, observed during treatment with the investigational product. Objective response rate is defined as the proportion of patients alive with objective response based on RECIST v1.1. Objective response is recorded from study treatment initiation until the end of treatment.
Time frame: an expected average of 6 months
24-weeks clinical benefit rate (CBR) independently for each cohort
CBR is defined as the proportion of patients with clinical benefit at 6 months. Clinical benefit is defined as confirmed complete response, confirmed partial response or stable disease more than 24 weeks, defined as per RECIST v1.1.
Time frame: 24 weeks
Best overall response (BoR) independently for each cohort
BoR is defined as the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation. The best overall response is determined once all the data for the participant is known (RECIST v1.1).
Time frame: Throughout the treatment period, an expected average of 6 months
Duration of response (DoR) independently for each cohort
DoR is defined as the time from documentation of tumor response (complete response/partial response whichever is first recorded) to disease progression, according to RECIST v1.1. DoR will be assessed in responder (confirmed CR / PR) patients only.
Time frame: Throughout the treatment period, an expected average of 6 months
1-year progression-free survival (PFS), independently for each cohort
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PFS is defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause), whichever occurs first
Time frame: 1 year
2-year progression-free survival (PFS), independently for each cohort
PFS is defined as the time from study treatment initiation to the first occurrence of disease progression or death (of any cause), whichever occurs first
Time frame: 2 year
1-year overall survival (OS), independently for each cohort
OS is defined as the time from study treatment initiation to death (of any cause)
Time frame: 1 year
2-year overall survival (OS), independently for each cohort
OS is defined as the time from study treatment initiation to death (of any cause)
Time frame: 2 year
Safety profile, independently for each cohort: Common Terminology Criteria for Adverse Events version 5
Number of participants with toxicity graded using the Common Terminology Criteria for Adverse Events version 5
Time frame: Throughout the treatment period, an expected average of 6 months
24-weeks clinical benefit rate (iCBR) independently for each cohort as per iRECIST
iCBR is defined as the rate of patients with iCR, iPR or immune stable disease (iSD)
Time frame: 24 weeks
Duration of response (iDoR) independently for each cohort as per iRECIST
iDoR is defined as the time from the date of the first response iCR/iPR (whichever is first recorded) to the date of PD (iUPD confirmed as iCPD) as per iRECIST. iDOR is defined for subjects with iCR or iPR. If a patient has iPR (#1) followed by a iUPD (#1) which is not confirmed, then a iPR (#2) followed by a iUPD (#2) which is confirmed at the next assessment, then the iDOR is calculated from iPR1 until iUPD2
Time frame: Throughout the treatment period, an expected average of 6 months
1-year progression-free survival (iPFS), independently for each cohort as per iRECIST
o iPFS is defined as the time from study treatment initiation to the first occurrence of disease progression as per iRECIST or death (of any cause), whichever occurs first. The event date to be used for calculation of progression-free survival (iPFS) should be the first date at which progression criteria are met (ie, the date of iUPD) provided that iCPD is confirmed at the next assessment. If iUPD occurs, but is disregarded because of later iSD, iPR, or iCR, that iUPD date should not be used as the progression event date. 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 timepoint responses are all iUPD, and iCPD never occurs
Time frame: 1 year
2-year progression-free survival (iPFS), independently for each cohort as per iRECIST
o iPFS is defined as the time from study treatment initiation to the first occurrence of disease progression as per iRECIST or death (of any cause), whichever occurs first. The event date to be used for calculation of progression-free survival (iPFS) should be the first date at which progression criteria are met (ie, the date of iUPD) provided that iCPD is confirmed at the next assessment. If iUPD occurs, but is disregarded because of later iSD, iPR, or iCR, that iUPD date should not be used as the progression event date. 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 timepoint responses are all iUPD, and iCPD never occurs
Time frame: 2 year
iORR independently for each cohort
iORR is defined as the rate of patients with immune complete or partial responses (iCR, iPR) as per iRECIST. iCR and iPR can be assigned after iUPD (immune unconfirmed progressive disease) has been documented as per iRECIST (Seymour et al)
Time frame: Throughout the treatment period, an expected average of 6 months