A Phase 1 Open-Label, First-in-human, Dose Escalation and Expansion Study to Determine the Safety, Tolerability, Dosimetry, Pharmacokinetics, and Preliminary Efficacy of 212Pb-DOTAM-GRPR1 in Adult Participants with Recurrent or Metastatic GRPR-expressing Tumors
In this open-label, dose escalation and dose expansion single ascending dose (SAD) and multiple ascending dose (MAD) phase 1 study, participants with recurrent or metastatic histologically confirmed GRPR-expressing tumors will be enrolled. In the dose escalation portion, a classic 3+3 design will be utilized for the SAD cohorts and a BOIN design for the MAD cohorts. Dose escalation may proceed until the recommended MAD dose is determined. Up to six (2 SAD and 4 MAD) cohorts are expected to be enrolled. Participants will be treated with up to four cycles administered every 4 or 6 weeks. Once the recommended MAD dose is determined, the expansion cohorts of the study will commence. A dosimetry sub study will also be conducted in participants part of the dose escalation.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
48
²¹²Pb-DOTAM-GRPR1 is a radioimmunoconjugate comprised of ²¹²Pb, the metal chelator DOTAM (1,4,7,10-Tetrakis(carbamoylmethyl)-1,4,7,10- tetraazacyclododecane) and a GRPR-targeted antagonist.
Northwestern University Robert H Lurie Medical Research
Chicago, Illinois, United States
RECRUITINGUK Markey Cancer Center
Lexington, Kentucky, United States
RECRUITINGAdvanced Molecular Imaging and Therapy
Glen Burnie, Maryland, United States
RECRUITINGXCancer Omaha / Urology Cancer Center
Omaha, Nebraska, United States
RECRUITINGTo determine the Recommended Phase 2 Dose (RP2D) of ²¹²Pb-DOTAM-GRPR1
Incidence of DLTs.
Time frame: 14 months
To assess the safety and tolerability of 212Pb-DOTAM-GRPR1.
Measured as Incidence and severity of TEAEs and TESAEs.
Time frame: 24 months
To assess the safety and tolerability of 203Pb-DOTAM-GRPR1.
Measured as Incidence and severity of TEAEs and TESAEs.
Time frame: 24 months
To assess PK of ²¹²Pb-DOTAM-GRPR1
212Pb-DOTAM-GRPR1 radioactivity concentration as a function of time in whole blood, plasma and urine
Time frame: 24 months
To evaluate the preliminary antitumor activity of 212Pb-DOTAM-GRPR1.
ORR by RECIST1.1, DOR, PFS by Investigator assessment and OS.
Time frame: 24 months
To evaluate the preliminary antitumor activity of 212Pb-DOTAM-GRPR1
For participants with mCRPC, by Investigator assessment of ORR which is defined as a proportion of participants having a 'best overall response' (BOR) assessment of Complete Response (CR) or Partial Response (PR) as per PCWG3 guidelines.
Time frame: 24 months
To evaluate the preliminary antitumor activity of 212Pb-DOTAM-GRPR1
For participants with mCRPC, by Investigator assessment of DOR which is defined as the time from the first documented objective response of PR or CR by PCWG3, whichever occurs earlier, to disease progression or death.
Time frame: 24 months
To evaluate the preliminary antitumor activity of 212Pb-DOTAM-GRPR1
For participants with mCRPC, by Investigator assessment of PFS which is defined as the time from the start of study intervention to the date of first observed disease progression (Investigator's radiological assessment), clinical disease progression (Investigator's assessment) or death due to any cause as per PCWG3 guidelines.
Time frame: 24 months
To evaluate the preliminary antitumor activity of 212Pb-DOTAM-GRPR1
For participants with mCRPC, as Overall Survival (OS) is defined as the time from the date of the start of study intervention to the date of death due to any cause.
Time frame: 24 months
To evaluate the preliminary antitumor activity of 212-PbDOTAM-GRPR1.
For participants with recurrent GBM, by Investigator assessment of ORR which is defined as a proportion of participants having a 'best overall response' (BOR) assessment of Complete Response (CR) or Partial Response (PR) as per RANO 2.0 criteria.
Time frame: 24 Months
To evaluate the preliminary antitumor activity of 212Pb-DOTAM-GRPR1.
For participants with recurrent GBM, by Investigator assessment of DOR defined as the time from the first documented objective response of PR or CR by RANO v 2.0, whichever occurs earlier, to disease progression or death
Time frame: 24 months
To evaluate the preliminary antitumor activity of 212Pb-DOTAM-GRPR1.
For participants with recurrent GBM, Investigator assessment of PFS defined as the time from the start of study intervention to the date of first observed disease progression (Investigator's radiological assessment), clinical disease progression (Investigator's assessment) or death due to any cause as per RANO 2.0 criteria.
Time frame: 24 months
To evaluate the preliminary antitumor activity of 212Pb-DOTAM-GRPR1.
For participants with recurrent GBM, Overall Survival (OS) is defined as the time from the date of the start of study intervention to the date of death due to any cause.
Time frame: 24 months
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