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A Randomized Phase II Non-Comparative Study of PF-04691502 and Gedatolisib (PF-05212384) in Patients With Recurrent Endometrial Cancer

A Randomized Phase II Non-Comparative Study of PF-04691502 and Gedatolisib (PF-05212384) in Patients With Recurrent Endometrial Cancer

Josep María Del Campo, Michael Birrer, Craig Davis, Keiichi Fujiwara, Ashwin Gollerkeri, Martin Gore, Brett Houk, Susie Lau, Andres Poveda, Antonio González-Martín, Carolyn Muller, Kei Muro, Kristen Pierce, etc.

Gynecol Oncol. 2016 Jul;142(1):62-69.

PMID: 27103175

Abstract:

Objective:
PF-04691502 and gedatolisib (PF-05212384) are potent, dual PI3K/mTOR inhibitors. This phase II study (B1271004) was conducted in patients with recurrent endometrial cancer following platinum-containing chemotherapy. The primary endpoint was to assess clinical benefit response (complete or partial response, or stable disease for ≥16weeks) following treatment with PF-04691502 or gedatolisib.
Methods:
The main study consisted of four independent arms based on a Simon two-stage design. Patients were assigned to putative PI3K-basal (PF-04691502 or gedatolisib) or PI3K-activated (PF-04691502 or gedatolisib) arms based on stathmin-low or stathmin-high tumor expression, respectively. Japanese patients were also enrolled in a separate lead-in cohort.
Results:
In stage 1 (main study), eighteen patients were randomized to PF-04691502 and 40 to gedatolisib. The two PF-04691502 arms were discontinued early due to unacceptable toxicity, including pneumonia and pneumonitis. The most common treatment-related adverse events associated with gedatolisib were nausea (53%), mucosal inflammation (50%), decreased appetite (40%), diarrhea (38%), fatigue (35%), and dysgeusia and vomiting (each 30%). Clinical benefit response rate was 53% (10/19) in the gedatolisib/stathmin-low arm and 26% (5/19) in the gedatolisib/stathmin-high arm. Safety profile and pharmacokinetic characteristics of both drugs in the Japanese lead-in cohort were comparable to the Western population.
Conclusions:
Gedatolisib administered by weekly intravenous infusion demonstrated acceptable tolerability and moderate activity in patients with recurrent endometrial cancer. PF-04691502 daily oral dosing was not well tolerated. Clinical benefit response criteria for proceeding to stage 2 were only met in the gedatolisib/stathmin-low arm. Stathmin-high expression did not correlate with greater treatment efficacy. ClinicalTrials.gov registration ID: NCT01420081.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1197160783	PF-05212384		1197160-78-3	Price

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