Thank you chuckles. I appreciate making this assessment on the Basket Trial.
For the Basket Trial, First Posted 8/7/2020, the Brief Summary states:
With this as the trial's protocol, should we not understand that dosing has been continued at least in these patients?
Same with the Compassionate Use trial, First Posted 3/18/2020:
Again, can we not understand that as per protocol, dosing has continued in these compassionate use patients?
Now, the Detailed Description for the Carboplatin Study, First Posted 2/12/2019, does not indicate the Until When, but rather divides the trial into its constituent phases:
But given the phrasing of the End Dates of the Basket Trial, your reasoning of going back 12 weeks seems to combine the two trials because there is no Phase 1 and Phase 2 in the Basket Trial, but it does discuss 12 weeks. The Basket trial is only a Phase 2 trial, so why did you subtract 12 weeks? Shouldn't you really be adding 12 weeks, or 3 months to the end of completion? For the reasons I explained above, I don't think dosing should have stopped as per trial protocol, but if it had stopped, the trial completion may have been November 7, 2021. Tracking of these patients would have continued up to February 7, 2022 which could give us an Overall Survivability of 15.5 months. But, as per the trial protocol, the medication should still be given, even today.
The Basket Trial Outcomes say:
So I see where the 12 weeks came from, but I think your application of it is off because Primary and Secondary is not Phase 1 and Phase 2. Primary and Secondary are referring to the goals of the trial where as Phase 1 & 2 are the type of trial where Phase 2 may be advanced to after successful completion of Phase 1 and could have been following a 12 week Phase 1 trial.
Regardless, because the beginning of the Basket Trial was in August 2020, these patients would be followed up to 2 years following completion of treatment. At worst case, completion of treatment was November 7, 2021. Hopefully, all of the patients are still treated, but we have no guarantee. So worst case, the patients as per trial protocol, would be followed until November 7, 2023.
For the Basket Trial, First Posted 8/7/2020, the Brief Summary states:
Quote:This is a single arm phase II study with 30 patients of leronlimab (PRO 140) in patients with CCR5+ locally advanced or metastatic solid tumors.
Leronlimab (PRO 140) will be administered subcutaneously as weekly dose of 525 mg until disease progression or intolerable toxicity. Subjects participating in this study will be allowed to receive/continue standard-of-care chemotherapy or radotherapy as per the dosing schedule included on the package insert.
In this study, patients will be evaluated for tumor response approximately every 3 months or according to institution's standard practice by CT, PET/CT or MRI with contrast (per treating investigator's discretion) using the same method as at baseline.
With this as the trial's protocol, should we not understand that dosing has been continued at least in these patients?
Same with the Compassionate Use trial, First Posted 3/18/2020:
Quote:Detailed Description:
This is a single arm, compassionate use study with 30 patients for leronlimab (PRO 140) combined with a treatment of physician's choice (TPC) in patients with CCR5+ mTNBC.
Leronlimab (PRO 140) will be administered subcutaneously as weekly dose of 350 mg until disease progression or intolerable toxicity. Treatment of Physician's Choice (TPC) is defined as one of the following single-agent chemotherapy drugs administrated according to local practice: eribulin, gemcitabine, capecitabine, paclitaxel, nab-paclitaxel, vinorelbine, ixabepilone, or carboplatin. The selected treatment should be administered as per the dosing schedule included on the package insert.
In this study, patients will be evaluated for tumor response approximately every 3 months or according to institution's standard practice by CT, PET/CT or MRI with contrast (per treating investigator's discretion) using the same method as at baseline. Tumor measurements will be done using RECIST v1.1.
Again, can we not understand that as per protocol, dosing has continued in these compassionate use patients?
Now, the Detailed Description for the Carboplatin Study, First Posted 2/12/2019, does not indicate the Until When, but rather divides the trial into its constituent phases:
Quote:Phase Ib
Phase Ib is a dose escalation phase with 3 dose levels (cohorts) of leronlimab (PRO 140) administered in combination with a fixed dose of carboplatin at AUC 5. This dose finding portion of study will follow a "3+3" designed to determine the maximum tolerated dose (MTD) of leronlimab (PRO 140) administered as subcutaneous injection in subjects with histologically confirmed mTNBC that express CCR5.
Phase II
Phase II is a single arm study with 30 patients in order to test the hypothesis that the combination of carboplatin AUC 5 intravenously and MTD of leronlimab (PRO 140) SC will increase PFS in patients with CCR5 + mTNBC.
But given the phrasing of the End Dates of the Basket Trial, your reasoning of going back 12 weeks seems to combine the two trials because there is no Phase 1 and Phase 2 in the Basket Trial, but it does discuss 12 weeks. The Basket trial is only a Phase 2 trial, so why did you subtract 12 weeks? Shouldn't you really be adding 12 weeks, or 3 months to the end of completion? For the reasons I explained above, I don't think dosing should have stopped as per trial protocol, but if it had stopped, the trial completion may have been November 7, 2021. Tracking of these patients would have continued up to February 7, 2022 which could give us an Overall Survivability of 15.5 months. But, as per the trial protocol, the medication should still be given, even today.
The Basket Trial Outcomes say:
Quote:
Primary Outcome Measures :
Number, frequency, and severity of adverse events (AEs) [ Time Frame: From the time of first treatment until 12 weeks after study treatment completion ]
Note: Adverse events will follow National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Incidence of abnormal laboratory tests results [ Time Frame: Up to 12 weeks after study treatment completion ]
Changes in Eastern Cooperative Oncology Group (ECOG) performance status from baseline to subsequent scheduled visits [ Time Frame: Up to 12 weeks after study treatment completion ]
Secondary Outcome Measures :
Progression free survival (PFS) defined as time in months from the date of first study treatment to the date of disease progression or death from any cause, whichever comes first. [ Time Frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment. ]
Note: All patients who receive at least one dose of leronlimab will be included in the primary analyses of PFS. The Response Evaluation Criteria in Solid Tumors (RECIST v1.1) criteria will be used for objective tumor response assessment (when disease is measurable and non- measurable);
Overall response rate (ORR, defined as CR + PR) in subjects with CCR5+ locally advanced or metastatic solid tumors treated with leronlimab [ Time Frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment. ]
Note: Overall response rate is defined as the proportion of patients who achieve an overall response of complete response or partial response in the total number of evaluable patients, assessed by RECIST v1.1. Clinical benefit rate is defined as the proportion of patients who achieve an overall response of complete response or partial response or stable disease in the total number of evaluable patients, assessed by RECIST v1.1.
Clinical Benefit Rate (CBR, defined as CR + PR + SD) in subjects with CCR5+ locally advanced or metastatic solid tumors treated with leronlimab [ Time Frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment. ]
Note: Overall response rate is defined as the proportion of patients who achieve an overall response of complete response or partial response in the total number of evaluable patients, assessed by RECIST v1.1. Clinical benefit rate is defined as the proportion of patients who achieve an overall response of complete response or partial response or stable disease in the total number of evaluable patients, assessed by RECIST v1.1.
Time to new metastases (TTNM) [ Time Frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. ]
Note: Recorded time from baseline metastatic disease (at time of enrollment) to the time of development of new metastasis in different site, assessed up to 6 months. New metastases in same site will be also recorded.
The change from baseline in circulating tumor cells (CTC) level in the peripheral blood. [ Time Frame: From date of first treatment until the date of first documented progression or date of death from any cause, whichever came first. ]
Note: Reported unit of measure will be the number of CTCs/milliliter. CTCs enumeration will be performed at baseline and at the time of response assessment, assessed up to 6 months. Fraction of baseline positive and change from ≥5 CTCs will be recorded and reported
Overall survival defined as time in months from the date of first study treatment to the date of death [ Time Frame: The time in months from start of treatment to progression or death will be measured for all patients who receive at least one dose of study drug. Patients will be followed up to 2 years after completion of treatment. ]
Note: Patients will be followed from the start of treatment until 2 years post-treatment or death, whichever occurs first, and average survival time will be measured.
So I see where the 12 weeks came from, but I think your application of it is off because Primary and Secondary is not Phase 1 and Phase 2. Primary and Secondary are referring to the goals of the trial where as Phase 1 & 2 are the type of trial where Phase 2 may be advanced to after successful completion of Phase 1 and could have been following a 12 week Phase 1 trial.
Regardless, because the beginning of the Basket Trial was in August 2020, these patients would be followed up to 2 years following completion of treatment. At worst case, completion of treatment was November 7, 2021. Hopefully, all of the patients are still treated, but we have no guarantee. So worst case, the patients as per trial protocol, would be followed until November 7, 2023.
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