Seven abstracts featuring Exelixis compounds will be presented in Chicago, IL at ASCO’s annual meeting from May 30 to June 3.
Links to data summaries available at time of presentation.
| Study |
ASCO Abstract Number |
ASCO Abstract Title |
Presentation Date & Time (CST) |
| XL647-002 |
3528 |
A phase 1 study of XL647, an EGFR, HER2, VEGFR2 inhibitor, administered orally daily to patients (pts) with advanced solid malignancies (ASM)
Data Summary |
5/31/08:
8am-12noon |
| XL880-201 |
5103 |
A phase 2 study of the dual MET/VEGFR2 inhibitor XL880 in patients (pts) with papillary renal carcinoma (PRC)
Data Summary |
5/31/08:
8am-12noon |
| XL765-001 |
3510 |
A phase 1 dose-escalation study of the safety, pharmacokinetics(PK) and pharmacodynamics (PD) of a novel PI3K inhibitor, XL765, administered orally to patients (pts) with advanced solid tumors
Data Summary |
5/31/08:
1:45-2:15pm |
| |
| XL184-001 |
3522 |
A phase 1 study of XL184, a RET, VEGFR2 & MET kinase inhibitor, in patients (pts) with advanced malignancies, including pts with medullary thyroid cancer (MTC)
Data Summary |
6/1/2008:
10-10:15am |
| XL647-201 |
8053 |
Activity of XL647 in clinically selected NSCLC patients (pts) enriched for the presence of EGFR mutations: Results from phase 2
Data Summary |
6/1/2008:
2:00-6:00pm |
| |
| XL647-203 |
8028 |
XL647 is active and well-tolerated in NSCLC patients with acquired resistance to EGFR-TKIs: preliminary results of a phase 2 trial
Data Summary |
6/2/2008:
8am-12noon |
| XL880-204 |
4572 |
Preliminary activity of XL880, a dual MET/VEGFR2 inhibitor, in MET amplified poorly differentiated gastric cancer (PDGC): Interim results of a multicenter phase 2 study
Data Summary |
6/2/2008:
8am-12noon |
XL647-002
Abstract #3528
SUMMARY
Preliminary data from an ongoing phase 1 clinical trial of XL647 in patients (pts) with advanced
solid tumors not amenable to standard therapies were reported at the 44th Annual Meeting of the
American Society of Clinical Oncology in May 2008.
- The study has enrolled 31 pts and is closed to enrollment.
- Pts received escalating dose levels of XL647 (75-350 mg) administered orally once daily.
- The MTD was determined to be 300 mg administered orally once daily.
- Three dose-limiting toxicities (DLTs) occurred.
- Two of 4 pts enrolled at 350 mg experienced DLTs of clinically asymptomatic Grade 3
QTc prolongation that were subsequently downgraded to Grade 2 following digital analysis
by central review. These pts were dose reduced to 300 mg and did not experience any
further DLTs.
- One event of Grade 3 study drug-induced pneumonitis occurred in 1 of 3 pts enrolled at
300 mg.
- The cohort was expanded, and no further DLTs were observed.
- The most common treatment-related adverse events were Grade 1 and 2 diarrhea, rash,
dysgeusia, and fatigue.
- Clinically asymptomatic QTc prolongation was observed as assessed using digital analysis by a
central ECG laboratory.
- Four subjects experienced a maximum of Grade 1, and 11 experienced Grade 2.
- Pharmacokinetic analysis:
- Exposure (AUC) increases approximately in proportion to the dose.
- XL647 accumulated approximately 4.2-fold in plasma with repeated daily dosing.
- Apparent steady-state plasma concentrations were reached by approximately Day 15.
- As of 9 May 2008, 16 of 30 evaluable pts achieved prolonged stable disease (>3 months),
5 of whom are currently on study.
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Abstract #5103
Data Summary Available via Webcast
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Abstract #3510
SUMMARY
Interim data from an ongoing phase 1 clinical trial of XL765 were reported at the 44th Annual
Meeting of the American Society of Clinical Oncology in May 2008. Nineteen patients (pts) have
been enrolled as of May 20, 2008.
- XL765 is being administered orally twice daily (BID) to pts with metastatic or unresectable solid
tumors for which known effective measures do not exist or are no longer effective.
- A once-daily regimen (QD) will also be evaluated.
- Doses up to 60 mg BID were generally well-tolerated with no dose-limiting toxicities (DLTs)
reported.
- DLTs of Grade 3 and 4 increased hepatic transaminases (n = 1 each), Grade 3 anorexia
(n = 1), and Grade 3 hypophosphatemia (n = 1) were reported at the maximum administered
dose of 120 mg BID.
- One case of Grade 1 hyperglycemia has also been reported at this dose level.
- Preliminary pharmacokinetic analyses indicate that AUC and Cmax appear to increase with
dose of XL765, the mean terminal phase half-life at steady state ranges from 3 to 11 hours,
and plasma concentrations appear to reach steady state by Day 8.
- Preliminary pharmacodynamic analyses indicate that XL765 administration is associated with
inhibition of the PI3K signaling pathway in pts.
- XL765 administration augments food-induced changes in plasma insulin in an exposure-dependent
fashion, but generally has no effect on plasma glucose levels.
- Reductions in phosphorylation of pathway components including PRAS40 and 4EBP1 were
observed in peripheral blood cells.
- Reductions in phosphorylation of AKT, PRAS40, 4EBP1, and S6 were observed in solid
tissues, including patient (pt) hair bulbs and skin.
- Reductions of 80-90% in the phosphorylation of AKT (both S473 and T308 phosphoepitopes),
4EBP1, and S6, and a 54% reduction in cell proliferation (as assessed by Ki67
staining) were observed in tumor tissue from a pt with chondrosarcoma at the 60 mg BID
dose level.
- The pattern of inhibition of PI3K pathway phosphoepitopes in these tissues suggests that
XL765 inhibits PI3K and both mTOR/raptor and mTOR/rictor in pts.
- Two pts (colon adenocarcinoma and mesothelioma) have had progression-free survival for
greater than six months.
- The maximum tolerated dose has not yet been established, and dose escalation is ongoing
for both BID and QD regimens.
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Abstract #3522
SUMMARY
Interim data from an ongoing phase 1 clinical trial of XL184 in adult patients (pts) with advanced
solid tumors not amenable to standard therapies were reported at the 44th Annual Meeting of
the American Society of Clinical Oncology in June 2008. There were 60 pts available for safety
and tumor response analyses as of the May 1, 2008 data cutoff; further data including tumor
response were also provided for 9 additional pts after the cutoff.
- Pts received escalating dose levels of XL184 administered orally on an intermittent schedule
(5 days on/9 days off) or a once daily schedule, and as either a suspension or a capsule
formulation.
- The maximum tolerated dose (MTD) was defined as 175 mg administered orally once daily
using capsules.
- An expanded cohort of >e; 20 pts with medullary thyroid cancer (MTC) is enrolling at the MTD.
- Anti-tumor activity has been observed in pts with various cancers, including MTC.
- Across all tumor types, ten pts had partial responses (PRs, 5 confirmed) and 25 pts had
stable disease (SD) >3 mo (range: 3+ to 22+ months).
- The best overall response rate in pts with MTC is 53%.
- The disease control rate (PR + SD > 3 months) in pts with MTC is 100%.
- XL184-related adverse events (AEs) in >e; 10% of pts include diarrhea, nausea, fatigue, mucositis,
anorexia, increased AST/ALT, anorexia, hypertension, vomiting, hair hypopigmentation, and
palmar-plantar erythema.
- Most AEs were Grade 1 and 2.
- DLTs included Grade 3 palmar/plantar erythema (n = 2), Grade 3 AST (n = 2) and ALT (n = 1)
elevation, Grade 3 lipase elevation (n = 1), and Grade 2 and 3 mucositis (n = 1 each).
- Pharmacodynamic analyses of plasma samples show statistically significant changes in
VEGF-A, sVEGFR2, and PIGF at the MTD.
- Pharmacokinetic analyses indicate a half-life of XL184 of 59 to 136 hours.
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Abstract #8053
SUMMARY
Data from an ongoing phase 2 clinical trial of XL647 in patients (pts) with previously untreated
non-small cell lung cancer (NSCLC) were reported at the 44th Annual Meeting of the American
Society of Clinical Oncology in June 2008.
- There were 41 pts treated with 350 mg of XL647 on the intermittent 5-days on/9-days off
dosing schedule, and 8 pts treated with 300 mg of XL647 on the daily dosing schedule.
- Pts with NSCLC were clinically selected based on adenocarcinoma histology and who had
either an activating EGFR mutation in tumor tissue, or met one of the following criteria: Asian,
female, or minimal smoking history.
- The clinical enrichment strategy identified ~30% of pts with EGFR activating mutations.
- There were 38 pts evaluable for response in the intermittent 5 on/9 off dosing schedule:
- Ten pts had partial responses (7 had EGFR activating mutations), and 17 pts had stable
disease (2 had EGFR activating mutations).
- XL647 demonstrated clinical benefit in 71% of pts in the intermittent 5 on/9 off schedule.
- All pts with EGFR activating mutations demonstrated clinical benefit (7 pts with partial
responses, 2 pts with stable disease).
- The median progression-free survival was 9.1 months in pts with activating EGFR mutations,
and 3.8 months in pts without detected EGFR mutations.
- Response assessment is too early for most pts enrolled in the daily dosing schedule.
- As of May 12, 2008, of 3 pts with at least one post baseline assessment, 2 pts experienced
a partial response (1 with an activating EGFR mutation) and 1 patient (pt) experienced
progressive disease.
- XL647 was generally well tolerated in this pt population.
- The most frequently reported treatment-related adverse events were Grade 1 and 2 diarrhea,
rash, and fatigue, and Grade 1 nausea.
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Abstract #8028
SUMMARY
Preliminary data from an ongoing phase 2 clinical trial of XL647 in patients (pts) with non-small cell
lung cancer who have progressed after prior benefit from treatment with gefitinib or erlotinib were
reported at the 44th Annual Meeting of the American Society of Clinical Oncology in June 2008.
- The study has enrolled 41 pts and is closed to enrollment.
- Twenty of 39 evaluable pts experienced disease control (1 PR and 19 SD).
- Three of 10 pts with EGFR T790M mutations experienced SD.
- Clinical selection of pts who relapse after prior benefit from erlotinib or gefitinib results in a
population enriched for the presence of EGFR T790M mutations.
- Plasma was obtained from all pts, and tumor tissue from a subset of pts for mutation analysis.
- EGFR T790M was detected in 10 of 37 pts analyzed.
- The most common XL647-related adverse events were Grade 1 and 2 diarrhea, rash, and
fatigue.
- Clinically asymptomatic QTc prolongation was observed as assessed using digital analysis by a
central laboratory.
- 5 patients experienced a maximum of Grade 1, 14 pts experienced Grade 2, and 2 pts
experienced Grade 3.
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Abstract #4572
Data Summary Available via Webcast
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