Table 1. Key preclinical studies and clinical trials for rituximab SC and trastuzumab SC (Del Nagro et al, 2010; Salar et al, 2010; US NIH, 2011; Ismael et al, 2012; Salar et al, 2012; Wynne et al, 2012).
| Population (n) | Phase | Outcome | Comment |
|---|---|---|---|
|
Rituximab | |||
| Cynomolgus monkeys (n=11) | Preclinical | Pharmacokinetics, B-cell depletion and CD20 target coverage (SC vs IV) | Rituximab SC has similar pharmacokinetics, B-cell depletion and CD20 target coverage to rituximab IV |
| Previously treated or untreated FL (n=124) | Phase Ib (BP22333; NCT00930514) (n=124) | Stage 1: pharmacokinetics (SC vs IV) | Rituximab SC 1400 mg calculated to be non-inferior to an IV dose of 375 mg m−2 |
| Stage 1: safety (SC vs IV) | Rituximab SC has comparable safety profile to rituximab IV | ||
| Phase Ib (BP22333; NCT00930514) (n=155) | Stage 2: pharmacokinetics of rituximab SC (1400 mg) vs IV | Ongoing (due to complete in 2013) | |
| Previously untreated FL (n=530) | Phase III (BO22334; NCT01200758) | Stage 1: pharmacokinetics (SC vs IV) | Ongoing |
| Stage 2: Safety (SC vs IV) | Ongoing | ||
| Previously untreated CLL (n=200) |
Phase I (BO25341; NCT01292603) |
Pharmacokinetics; safety (SC vs IV) |
Ongoing |
|
Trastuzumab | |||
| HMV (n=24) and patients with HER2-positive EBC (n=42) | Phase I/Ib (BP22023; NCT00800436) | Pharmacokinetics | Trastuzumab SC (8 mg kg−1) provides comparable exposure to trastuzumab IV (6 mg kg−1) |
| Safety | There were fewer AEs with trastuzumab SC than IV | ||
| Neoadjuvant HER2-positive EBC (n=595) | Phase III (HannaH; NCT00950300) | Pharmacokinetics; efficacy; safety | Co-primary efficacy and pharmacokinetic end points met |
| HMV (n=119) | Phase I (CP3; NCT01344863) | Pharmacokinetics of the injection system vs manual injection | Study complete, data expected in 2012 |
| HER2-positive EBC patients who have completed (neo)adjuvant chemotherapy (n=400) | PrefHer | Patient preference; HCP satisfaction; HCP-perceived time savings; safety | Ongoing (due to complete in 2013) |
| HER2-positive EBC (n=2500) | SafeHer | Safety of repeated SC injections | Start March 2012 |
Abbreviations: AEs=adverse events; CLL=chronic lymphocytic leukaemia; EBC=early breast cancer; EBCC=European Breast Cancer Conference; FL=follicular lymphoma; HannaH=Enhanced Treatment With Neoadjuvant Herceptin study; HCP=health-care provider; HMV=healthy male volunteers; IV=intravenous; PrefHer=Preferences for Herceptin; SafeHer=Safety and Tolerability Study of Assisted- and Self-administered Therapy in Patients With Early HER2-Positive Breast Cancer; SC=subcutaneous.