Table 1 Clinical trials of inotuzumab ozogamicin (INO)

[55]

2

R/R Ph-Negative CD22 positive ALL

Mini-Hyper-CVD with INO and Rituximab

ORR was 78% (59% CR) MRD negative rates of 52% (at time of morphological response) and 82% (at 3 months).

Median RFS of 8 months.

11 months

VOD (15%); prolonged thrombocytopenia (81%); 95% suffered hepatotoxicity (20% with grade 3 or higher)

[63]

3

Refractory or Relapsed ALL

0.8 mg/m2 (D1), 0.5 mg/m2 (D8), 0.5 mg/m2 (D15)

Versus

Standard therapy

CR + CRi 80.7% (CR 35.8%)

5 months

7.7 months

Grade 3 or more thrombocytopenia, hepatotoxicity and VOD (11%)

[78]

1/2

R/R ALL

1.8 mg/m2 weekly

69% CR/CRi (29% CR)

cytopenias and liver toxicity

[84]

1

R/R FL (100%)

Single agent

1.3 mg/m2 q28d with dose escalation up to MTD 1.8 mg/m2 q28d

CR: 54%

ORR: 85%

–

–

No DLTs. MTD of 1.8 mg/m2 confirmed in Japanese population.

[85]

1/2

CD20 and CD22 positive B-NHL. Relapsed follicular lymphoma (35%), Relapsed diffuse large B-cell lymphoma (39%), or refractory aggressive NHL (25%)

Dose escalation (0.8, 1.3 and 1.8 mg/m2) study in combination with Rituximab 375 mg/m2

MTD of determined to be 1.8 mg/m2.

FL: 87% (62%)

DLBCL: 74% (50%)

Refractory: 20%

FL: NR (2 year PFS rate of 68%)

DLBCL: 17.1 months

Refractory: 1.9 months.

FL: 2 year OS rate 90%

DLBCL: 3 year OS rate 69%

Refractory: 8.8 months

Grade 3 to 4 thrombocytopenia (31%) and neutropenia (22%). SAEs of Pneumonia (4%), Sepsis (3%) and liver dysfunction (4%). No VOD.

[86]

1

B-NHL (CD20 and CD22-positive, B-cell NHL which has progressed after 1 or 2 prior therapies)

1.8 mg/m2, IV on day 2 of each 28 day cycle; up to 8 cycles + R 375 mg/m2, IV on day 1 of each 28 day cycle; up to 8 cycles

80% (60%)

NR

NR

90% SAEs, with thrombocytopenia, neutropenia, elevated liver enzymes and hypophosphatemia

[87]

1

CD22 positive NHL with at least 1 prior treatment

INO (0.8 mg/m2) + RCVP

84% (24%)

14.4 months

24.5 months

1 death due to neutropenic pneumonia in INO-CVP arm. (13/48) 27% discontinued therapy in INO-CVP arm due to adverse effects

[88]

1/2

CD22 positive NHL with at least 1 prior treatment; DLBCL (38%) FL (25%) MCL (24%) Refractory (42%)

INO (0.8 mg/m2) + R- GDP

Phase 1: 53% (20%);

6 m: 58%

12 m: 37%

24 m: 24%

6 m:81%

12 m: 61%

24 m: 55%

Grade 3 or more thrombocytopenia (75%); neutropenia (62%). One patient with grade 3 VOD.

Phase 2 dose (RP2D): 50% (14%)

Refractory: 35%