Table 1.
Clinical trials of inotuzumab ozogamicin (INO)
| Reference | Phase | Disease | Intervention INO + | ORR (CR) | mPFS | mOS | Significant toxicities |
|---|---|---|---|---|---|---|---|
| [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% |
Abbreviations: R/R refractory /relapsed, CVD cyclophosphamide vincristine dexamethasone, m month, ORR overall response rate, CR complete remission, PFS progression free survival, OS overall survival, RFS relapse free survival, VOD veno-occlusive disease, NHL non-Hodgkin lymphoma, NR not reached, MRD minimal residual disease, MTD maximal tolerated dose, SAE serious adverse event, DLBCL diffuse large B cell lymphoma, FL follicular lymphoma, MCL mantle cell lymphoma, RP2D recommended phase 2 dose, GDP gemcitabine dexamethasone cisplatin