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A Phase 1, Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas

Phase 1
18 Years
Open (Enrolling)
Advanced Solid Tumor, Lymphoma

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Trial Information

A Phase 1, Open-Label, Multiple Ascending Dose Study of DS-3078a, an Oral TORC1/2 Kinase Inhibitor, in Subjects With Advanced Solid Tumors or Lymphomas

This is a Phase 1, open-label study of DS-3078a to assess safety and tolerability, identify
the maximum tolerated dose (MTD) and tentative recommended phase 2 dose (RP2D), and assess
pharmacokinetic and pharmacodynamic properties in subjects with advanced solid tumor
malignancies or lymphomas. The study will include 2 parts: Dose Escalation and Dose

Inclusion Criteria:

- A pathologically or cytologically documented advanced solid tumor or lymphoma that
has relapsed from or is refractory to standard treatment or for which no standard
treatment is available.

- Men or women >=18 years old.

- Eastern Cooperative Oncology Group (ECOG) performance status =<1

- Have adequate bone marrow function, defined as:

- Platelet count >=100 x 10^9/L for solid tumors and >=75 x 10^9/L for lymphomas,

- Hemoglobin level >=9.0 g/dL, and ANC >=1.5 x 10^9/L for solid tumors and >=1.0 x
10^9/L for lymphomas.

- Have adequate renal function, defined as:

Creatinine clearance >=60 mL/min, or creatinine =<1.5 x ULN.

- Have adequate hepatic function, defined as:

- AST/ALT levels =<3 x ULN (=<5 x ULN if liver metastases are present) and

- Bilirubin =<1.5 x ULN.

- Have adequate blood clotting function, defined as prothrombin time and activated
partial thromboplastin time =<1.5 x ULN.

- Subjects must be fully informed about their illness and the investigational nature of
the study protocol (including foreseeable risks and possible side effects) and must
sign and date an Institutional Review Board/Ethics Committee-approved informed
consent form (including Health Insurance Portability and Accountability Act
authorization, if applicable) before performance of any study specific procedures or

For Part 2

- A pathologically or cytologically documented advanced solid tumor or non-Hodgkin
lymphoma, with measurable disease based on RECIST 1.1 or revised IWG criteria, that
is refractory to standard treatment. The solid tumor types that will be included in
the study are of the following kinds in which the mTOR signaling is frequently
activated: endometrial, prostate, breast, gastric, cervical,ovarian, or
neuroendocrine cancers, soft-tissue sarcoma, squamous cell NSCLC,renal cell carcinoma
or other tumor types approved by the Sponsor.

- Agree to undergo pre- and post-treatment tumor biopsies.

Exclusion Criteria:

- History of primary central nervous system malignancies

- Gastrointestinal diseases that could affect the absorption of DS-3078a in the opinion
of the Investigator

- Subjects with a fasting glucose >126 mg/dL (>7 mmol/L)

- History of diabetes mellitus (type 1 or 2) or glycosylated hemoglobin >7.0% at

- Positive test for hepatitis B surface antigen or hepatitis C antibody

- Recipient of live vaccine within 1 month of or during study drug treatment

- Use of chronic systemic corticosteroids (use of nasal or inhaled steroids is

- Subjects requiring daily supplemental oxygen

- Recipient of an allogenic stem cell or bone marrow transplant

- Presence of a concomitant medical condition that would increase the risk of toxicity,
in the opinion of the Investigator or Sponsor

- Clinically active brain metastases, defined as untreated and symptomatic, or
requiring therapy with steroids or anticonvulsants to control associated symptoms.

- Has unresolved toxicities from previous anticancer therapy, defined as toxicities
(other than alopecia) not yet resolved to NCI-CTCAE v4 grade =<1 or baseline.

- Systemic treatment with anticancer therapy, antibody-based therapy, retinoid therapy,
or hormonal therapy within 3 weeks before study drug treatment; or treatment with
nitrosoureas or mitomycin C within 6 weeks before study drug treatment; or treatment
with small-molecule targeted agents within 2 weeks or 5 half-lives before study drug
treatment, whichever is longer.

- Therapeutic radiation or major surgery within 4 weeks before study drug treatment or
palliative radiation therapy within 2 weeks before study drug treatment

- Participation in a clinical study within 3 weeks (2 weeks or 5 half-lives, whichever
is longer, for small-molecule targeted agents) before study drug treatment, or
current participation in other investigational procedures

- Concomitant treatment with strong inhibitors or inducers of cytochrome P450 3A4 and P

- Less than 1 week since using systemically acting drugs that increase gastric pH, such
as H2-blockers and proton pump inhibitors. Antacids should be avoided within 48
hours of the first dose of DS 3078a

- Prolongation of corrected QT interval by Fridericia's method (QTcF) at rest, where
the mean QTcF interval is >450 msec based on triplicate electrocardiogram (ECG)

- Pregnant or breastfeeding

- Substance abuse or medical, psychological, or social conditions that, in the opinion
of the Investigator, may interfere with the subject's participation in the clinical
study or evaluation of the clinical study results

For Part 2

- Subjects who have had prior treatment with an mTOR catalytic site inhibitor or dual
PI3K/mTOR inhibitor (including, but not limited to, OSI-027, INK128, ADZ8055,AZD2014,
WYE12513, PP242, BEZ-235, DS-7423, XL765, GDC-0980, SF1126, GSK2126458, PF4691502,
and PF05212384) will be disqualified from entering the study.

Type of Study:


Study Design:

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Description:

To determine the maximum tolerated dose (MTD) and tentative recommended Phase 2 dose (RP2D) of DS 3078a

Outcome Time Frame:

3 years

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

April 2012

Completion Date:

April 2015

Related Keywords:

  • Advanced Solid Tumor
  • Lymphoma
  • endometrial
  • prostate
  • breast
  • gastric
  • cervical
  • ovarian
  • neuroendocrine cancers
  • soft-tissue sarcoma
  • squamous cell NSCLC
  • renal cell carcinoma
  • non-Hodgkin lymphoma
  • Lymphoma
  • Neoplasms



South Texas Accelerated Research Therapeutics San Antonio, Texas  78229