The Genesis of the Antibody Conjugate Gemtuzumab Ozogamicin (Mylotarg) for Acute Myeloid Leukemia - Accounts in Drug Discovery Case Studies in Medicinal Chemistry - page 111

100

Doses given
days 7, 11, & 15

Total Doses

80

0.5 ug x 3
1 ug x 3
3 ug x 3
6 ug x 3

(75 ug/kg)

(150 ug/kg)

(450 ug/kg)

60

(900 ug/kg)

40

20

0

hP67.6-Conj MOPC-Conj

2/5 deaths in the 900 ug/kg dose group
for the hP67.6 conjugates, no deaths in
the lower dose groups.

5/5 deaths in the 900 ug/kg dose group
for the MOPC conjugate, 2/5 deaths in
the 450 ug/kg dose group

Figure 5.7 Gemtuzumab ozogamicin in vivo activity. Subcutaneous tumor implants
were allowed to grow to an average size of about 150mg prior to treat-
ment as indicated. Results shown are at day 34. Tumors were absent in 4/5
animals at the lowest three doses and 5/5 at the highest dose of hP67.6-
Conj (gemtuzumab ozogamicin) and did not regrow for over 100 days in
the surviving animals. (The top dose of 900 mgkg 1 was well tolerated in
most other experiments.) No animals were tumor-free in the MOPC-Conj
group, a non-binding control conjugate.

Figure 5.8 Gemtuzumab ozogamicin ex vivo activity. Bone marrow samples from
AML patients were plated in the presence of either gemtuzumab ozoga-
micin or an isotype-matched, non-binding control conjugate. The num-
bers of colonies formed were counted for each sample and are plotted in
order of increasing ratio, expressed as a percent.