XL647 and SB37 – pro

You are in a phase I study of a novel drug. XL647 is an orally bioavailable small molecule inhibitor of HER2, EGFR, VEGFR and EphB4. Study results demonstrate that XL647 is well tolerated and shows evidence of biologic and clinical activity. A maximum tolerated dose (MTD) has been identified. Results of the Phase I trial of XL647 were presented in a poster, titled “A Phase I Dose-Escalation and Pharmacokinetic (PK) Study of a Novel Spectrum Selective Kinase Inhibitor, XL647, in Patients with Advanced Solid Malignancies (ASM),” (Abstract # 3044) in a poster discussion session at the 42nd Annual Meeting of the American Society of Clinical Oncology (ASCO). The conference is taking place June 2 to 6 in Atlanta.

As of March 15, 2006, a total of 40 patients have been treated across 9 dose levels ranging from 0.06 to 7.0 mg/kg, in a liquid formulation and then a tablet formulation and are evaluable for safety endpoints.

As reported by the investigators one patient (non-small cell lung cancer [NSCLC]) has had a partial response and 12 others (NSCLC [3], chordoma [2], adenoid cystic carcinoma [2], adrenocortical carcinoma, colorectal, ovarian, mesothelioma and head and neck cancer) have had prolonged stable disease >3.5 months. Updated phase 2 data continue to show encouraging anti-tumor activity in non- small cell lung cancer. Consistent with data from the phase 2 study reported in September 2007 at the 12th International Association for the Study of Lung Cancer World
Conference on Lung Cancer, 68% of the 34 patients evaluable for tumor
response had clinical benefit: 10 patients had partial responses (eight
confirmed, two not yet confirmed), and 13 patients had stable disease as
their best response. All seven patients with activating EGFR mutations
experienced tumor shrinkage (six PRs and one SD), and three patients with
wild type EGFR achieved partial responses (Abstract #B124). XL647 was
generally well tolerated in this patient population.
Additionally, data from a phase 1 dose-escalation study evaluating
daily dosing of XL647 were presented (Abstract #B242). As of August 8,
2007, this study had enrolled 26 patients with a variety of advanced solid
tumors. 11 of 21 patients assessable for tumor response receiving doses of
XL647 ranging from 75 to 300 mg achieved stable disease for at least three
months. The XL647 exposure with daily dosing at the maximum tolerated dose
(MTD) (300 mg) in this study was approximately twofold higher over a 28-day
cycle compared to the exposure observed previously at the MTD (350 mg) for
the intermittent dosing regimen. XL647 was generally well tolerated and
related Grade 3 adverse events were infrequent. No Grade 3 or greater skin
rash was reported in this study. Pharmacodynamic analyses were conducted in
plasma samples and eyebrow hair follicles. Biomarker changes consistent
with EGFR inhibition were observed in eyebrow hair follicles following
XL647 treatment.

The study in which you enrolled is a Phase I dose finding study. Phase I studies by definition are not therapeutic in intent but are designed to find the maximally tolerated dose. The langauge os SB27 is contradictory on this point since it mandates coverage for phase I studies at the same time as it states: “For an enrollee diagnosed with cancer and accepted
into a phase I, phase II, phase III, or phase IV clinical trial for
cancer, every health care service plan contract, except a specialized
health care service plan contract, that is issued, amended,
delivered, or renewed in this state, shall provide coverage for all
routine patient care costs related to the clinical trial if the
enrollee’s treating physician, who is providing covered health care
services to the enrollee under the enrollee’s health benefit plan
contract, recommends participation in the clinical trial after
determining that participation in the clinical trial has a meaningful
potential to benefit the enrollee. For purposes of this section, a
clinical trial’s endpoints shall not be defined exclusively to test
toxicity, but shall have a therapeutic intent.: The correct interpretation of this langauge in my opinion is that Phase I trials are only included when there is a specifically stated therapeutic intent as the later sentences of the above paragraph modify the first sentence. As such, I do not find that SB37 covers this trial.

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