First in Man Study Investigating the Biodistribution, the Safety and Optimal Recommended Dose of a New Radiolabelled Monoclonal Antibody Targeting Frizzled Homolog 10 (FZD10) in Patients With Relapsed or Refractory Non Resectable Synovial Sarcomas
PART 1: Imaging with OTSA101 DTPA-111In OTSA101-DTPA-111In (1.5mg OTSA101-DTPA radiolabeled
with 185 MBq of 11In) will be administered intravenously (IV) as a single injection on Day
-28 (D-28). Patients will undergo serial anterior-posterior gamma scans and single photon
emission computed tomography (SPECT/CT) at 1, 2, 5, 24, 48, 72, 144 hours post-dosing to
estimate absorbed radiation doses to tumor, to normal organs (i.e., liver, lung, kidney, and
bone marrow), and whole body in order to determine OTSA101-DTPA-111In tumor uptake (ID%/g [%
of injected dose (ID) per gram of tumor]) and biodistribution (ratio tumor/normal tissue of
estimated radiation-absorbed dose). PK sampling will be performed at the same time points
with additional sampling at D-14 and D0.
A Steering Committee meeting is planned at the end of PART 1 for each patient. The Steering
Committee will evaluate on a case by case basis at Day -7 for each patient if he/she can
proceed to the therapeutic part based on tumor targeting, biodistribution, safety and
- Patients with expected biodistribution and tumor uptake, no safety concerns and no
overt signs of disease progression will proceed to the therapeutic part of the study
after validation by the Steering Committee.
- Patients displaying abnormal/unexpected biodistribution of OTSA101-DTPA-111In, safety
concerns and/or overt sign of disease progression will be taken off the study and other
therapeutic plan will be envisaged.
PART 2: Therapeutic dose of OTSA101-DTPA-90Y OTSA101-DTPA-90Y will be administered IV as a
single injection on Day 0 (i.e. 28 days after the injection of OTSA101-DTPA-111In - A
1week-delay [i.e. +7 days] is authorized from the planned D0).
Twelve (12) patients should be randomized in the PART 2 and treated with OTSA101-DTPA-90Y at
two initial dose levels (6 patients per dose level):
- Arm A: 1.5 mg of OTSA101-DTPA radiolabeled with 370MBq of 90Y (Dose level 1 (DL1)
- Arm B: 1.5 mg of OTSA101-DTPA radiolabeled with 1110 MBq of 90Y (Dose level 2 (DL2)
Based on safety and preliminary efficacy data, a third dose level will be evaluated in 6
- Arm C: 3 mg of OTSA101-DTPA radiolabeled with 2220 MBq of 90Y (Dose level 3 (DL3).
Such a study design will allow the determination of an optimal and recommended dose,
surrounded by a lower suboptimal dose and a higher maximal tolerated (or possibly toxic)
The first 3 patients will be enrolled at Centre Léon Bérard. Following the randomization of
the first 2 patients, the accrual will be stopped for a maximal period of 1 month. The
safety data will be reviewed every 2 randomized patients. Thee benefit/risk ratio will be
regularly reviewed by the iDSMB and the Steering Committee (See Section Study Committee).
A compassionate program is planned for all randomized patients who derive clinical benefit
from the study drug (at least stable disease and acceptable tolerance). A maximum of 4
injections per year will be planned. Subsequent injection will be performed provided that
the eligibility criteria (except criteria related to previous treatment) are met before the
day of administration. All inclusion in the compassionate program will be validated by the
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Part 1: Biodistribution and binding of OTSA101-DTPA-111In
Limiting Event is defined as unacceptable/unexpected biodistribution/binding of the mAb, and/or absence of tumor uptake. Data review will be performed on a patient per patient basis. The Biodistribution and binding of OTSA101-DTPA-111In will be analyzed. The rate of Limiting Event will be summarized by a proportion together with its 95% confidence interval.
144 hours post-dose (dose administered at day -28)
Jean-Yves BLAY, MD, PhD
Centre Léon Bérard
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)