Phase II of combined Herceptin and Tykerb Trial?

[alw]

Hello - Has anyone seen the status of the Phase II trial for combined Herceptin and Tykerb? The Phase I is below from Dec 2005. I don't see a metion of Phase II in the ASCO 2007 Annual Meeting Agenda. Maybe at a later meeting?

With warm regards and hope,

Amy

[1073] A phase I, open-label study of the safety, tolerability and pharmacokinetics of lapatinib (GW572016) in combination with trastuzumab.

Storniolo AM, Burris III HA, Overmoyer B, Silverman P, Pegram MD, Jones SF, Peacock NW, Loftiss J, Koch KM, Paul E, Ho PTC. Indiana University Cancer Center, Indianpolis, IN; Sarah Cannon Cancer Center, Nashville, TN; Ireland Cancer Center, Cleveland, OH; UCLA Center for the Health Sciences, Los Angeles, CA; GSK, RTP, NC

ErbB1 and ErbB2 receptor expression in tumors predicts a poor outcome. Lapatinib is a potent oral ErbB1/ErbB2 receptor tyrosine kinase inhibitor. A novel approach to the treatment of breast cancer is the combination of trastuzumab and lapatinib, which may enhance cytostatic action by inactivation of ErbB2 through two different molecular mechanisms. In vitro data indicate synergistic activity of lapatinib in combination with trastuzumab in ErbB2 positive breast cancer cells.
Patients (pts) with advanced or metastatic breast cancer that overexpressed the ErbB2 protein 2+ or 3+, confirmed by either IHC and/or FISH were enrolled. Escalating dose levels of lapatinib (750 - 1500 mg/d) were administered once daily in combination with weekly, standard dose of trastuzumab (4 mg/kg loading dose followed by weekly 2 mg/kg infusions). Three pts were treated at each dose level, with expansion to 6 in the event of dose-limiting toxicity. Limited and full pharmacokinetic samples were obtained. Assessments of clinical response per RECIST criteria were performed at week 8 and then every 8 weeks. Cardiac safety assessments include collecting left ventricular ejection fraction (LVEF) by MUGA or ECHO, and 12-lead ECG at week 4, 8 and then every 8 weeks.
54 pts were treated, 27 in the dose escalation phase (cohort 750 - 3; cohort 1000 - 11; cohort 1250 10, cohort 1500 - 3) and 27 in the PK phase (cohort 1000). Median age was 53 years (range 30-80). A median of 4 treatment periods (1 treatment period = 4 weeks) were administered (range 1-15). G1-2 diarrhea, anorexia, fatigue and rash were the common toxicities. One incidence each of dose-limiting G3 fatigue and G3 nausea was reported separately at the 1500 mg/d dose level. No symptomatic declines in LVEF were reported at any dose level. In the dose escalation phase there was 1 CR, 5 PRs and 4 SDs > 6 months. In the PK phase there were 2 PRs and 4 SD > 6 months. The median number of prior chemotherapy regimens, in the responding pts, was 3 (range 1-4) and prior trastuzumab (monotherapy or in combination) was 4 (range 1-7).
The combination of lapatinib and trastuzumab showed significant clinical activity in this heavily pretreated population. The proposed phase II/III dose for this combination is 1000 mg lapatinib and standard doses of weekly trastuzumab. The clinical data support the synergism of lapatinib and trastuzumab noted in preclinical studies with ErbB2 overexpressing breast cancer cells. Additional randomized studies are planned with lapatinib and trastuzumab.

Thursday, December 8, 2005 5:00 PM