Interim analysis of toxicity and response in phase 1 trial of systemic targeted alpha therapy for metastatic melanoma.
OBJECTIVE
The aim is to assess toxicity and response of systemic alpha therapy for metastatic melanoma.


METHODS
This is an open-labelled Phase 1 dose escalation study to establish the effective dose of the alpha-immunoconjugate (213)Bi-cDTPA-9.2.27 mAb (AIC). Tools used to investigate the effects were physical examination; imaging of tumors; pathology; GFR; CT and changes in tumor marker. Responses were assessed using RECIST criteria.


CONCLUSIONS
Twenty-two patients with stage IV melanoma/in-transit metastasis were treated with activities of 55-947 MBq. Using RECIST criteria 50% showed stable disease and 14% showed partial response. One patient (6%) showed near complete response and was retreated because of an excellent response to the initial treatment. Another patient showed response in his tumor on mandible and reduction in lung lesions. Overall 30% showed progressive disease. The tumor marker melanoma inhibitory activity protein (MIA) showed reductions over eight weeks in most of the patients. The disparity of dose with responders is discussed. No toxicity was observed over the range of administered activities.


CONCLUSIONS
Observation of responses without any toxicity indicates that targeted alpha therapy has the potential to be a safe and effective therapeutic approach for metastatic melanoma.
Raja
Chand
C
CERO, St. George Hospital, Kogarah, Australia.
Graham
Peter
P
Abbas Rizvi
Syed M
SM
Song
Emma
E
Goldsmith
Helen
H
Thompson
John
J
Bosserhoff
Anja
A
Morgenstern
Alfred
A
Apostolidis
Christos
C
Kearsley
John
J
Reisfeld
Ralph
R
Allen
Barry J
BJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D004369:Pentetic Acid / Q000737:chemistry*; D015899:Tomography, Emission-Computed, Single-Photon
C528533:213Bi-cDTPA-9.2.27 monoclonal antibody; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004369:Pentetic Acid