A Phase 1/2, Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of Oral Rociletinib in Patients With Previously Treated Mutant EGFR Non-Small Cell Lung Cancer (NSCLC)
Lung cancer remains the most common cancer worldwide with non-small cell lung cancer
accounting for 85% of cases. Cytotoxic chemotherapy has been the mainstay of patients with
NSCLC; however, survival rates remain low and toxicity is significant. Molecularly targeted
therapies have proven to be superior to chemotherapy for NSCLC patients whose tumors have
mutations in EGFR. Recent studies have established tyrosine kinase inhibitors (TKIs) as the
gold standard for treating EGFR-mutation-positive NCSLC. However, patients on TKIs
eventually progress, and in approximately 50% of cases, progression is due to development of
an additional mutation called T790M. There are currently no approved therapies for patients
who progress on TKIs. Rociletinib may provide an effective therapy for a patient population
with few alternative treatment options. Nonclinical data demonstrate that rociletinib
inhibits T790M. It is anticipated that rociletinib may promote cell death in tumor cells
with the T790M mutation, thus providing possible therapeutic benefit in patients who have
developed T790M-mediated resistance to first generation TKIs.
This is a two-part, open-label study of oral rociletinib administered daily in previously
treated NSCLC patients who have documented evidence of an activating mutation in the EGFR
gene and have failed treatment with an EGFR inhibitor such as erlotinib, gefitinib or
afatinib.
This study will include 2 parts:
Phase 1 (completed enrolment): Dose-escalation Period with 21-day cycles; optional Treatment
Extension Period starting on Day 22
Phase 2 (currently enrolling): Evaluation of activity and safety in patients with the T790M
EGFR mutation who have:
Cohort A - Progressed on EGFR directed therapy (irrespective of the number and order of
previous lines of NSCLC therapy) or Cohort B - Progression on the first single agent EGFR
directed therapy received and also had no more than one previous line of chemotherapy
Phase I Open Label, Multi-center, Dose-escalation Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered CUDC-907, a PI3K and HDAC Inhibitor, in Subjects With Refractory or Relapsed Lymphoma or Multiple Myeloma
This is a Phase I, open-label, multi-center dose-escalation trial evaluating the safety and
tolerability of CUDC-907 as a single agent administered orally, once daily, to patients with
relapsed or refractory lymphoma or multiple myeloma. The following dosing schedules may be
examined, all consisting of 21-day cycles and including:
(i) continuous once daily (QD), (ii) twice weekly on Days 1, 4, 8, 11, 15, 18 (BIW) (iii)
thrice weekly on Days 1, 3, 5, 8, 10, 12, 15, 17, 19 (TIW) (iv) four days on/three days off
on Days 1-4, 8-11, and 15-18 (4/3), and (v) five days on/two days off on Days 1-5, 8-12, and
15-19 (5/2)
Sequential dose escalation cohorts of oral CUDC-907 are planned. Subject enrollment and dose
escalation will proceed according to a standard 3+3 design. In the absence of DLT, each
subject will be treated for a minimum of 21 days, and may continue to receive additional
treatment until disease progression has been documented or other treatment discontinuation
criteria have been met.
MTD or BED expansion cohorts of up to 36 evaluable (e.g., up to 12 subjects in each of 2 or
3 specific tumor types or subtype) to better define the safety, tolerability and preliminary
antitumor and pharmacodynamic activity of the study treatment, as well as suitability as an
RP2D and schedule.
Safety and tolerability will be assessed by the incidence and severity of adverse events as
determined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
(CTCAE v4.03). A Safety Review Committee (SRC) comprised of the Medical Monitor, Principal
Investigators, and Sponsor representatives, will be convened to review safety information
and to decide upon dose escalation and further subject enrollment.
The antitumor activity of study treatment will be assessed according to standard response
criteria as appropriate for each individual subject's tumor type (e.g., Revised Response
Criteria for Malignant Lymphoma and the International Uniform Response Criteria for Multiple
Myeloma).
Exploratory biological markers of activity will be assessed in peripheral blood mononuclear
cells (PBMC), plasma and tissue specimens (skin, tumor and bone marrow samples, where
available).
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