Summary

for people ages 18 years and up (full criteria)
at UCSD
study started
estimated completion

Description

Summary

The primary objective of this study is to evaluate the safety and tolerability of TAK-981 as a single agent in participants with advanced or metastatic solid tumors or lymphomas.

Official Title

An Open Label, Dose-Escalation Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of TAK-981 in Adult Patients With Metastatic Solid Tumors or Lymphomas

Details

The drug being tested in this study is called TAK-981. TAK-981 is being tested to evaluate safety, tolerability, and PK in participants who have locally advanced or metastatic solid tumors or relapsed or refractory lymphomas for whom there is no standard therapeutic alternative with established clinical benefit is available. The study will include a dose escalation phase and a dose expansion phase.

The study will enroll approximately 80 participants, approximately 40 to 50 participants in the dose escalation phase and approximately 15 participants in each of the 2 cohorts of dose expansion phase.

In the dose escalation phase, dose levels will be escalated based on safety, and available PK and pharmacodynamic data. This study will also determine the single agent recommended phase 2 dose (RP2D). Participants in dose expansion phase will be enrolled, once maximum tolerated dose (MTD) or biological effective dose (BED) is determined. One of the 2 cohorts in dose expansion phase will consist of participants with relapsed/refractory lymphomas, and other cohort will consist of participants with solid tumors with no standard therapeutic option available with established clinical benefit.

This multi-center trial will be conducted in the United States and Canada. The overall time to participate in this study is approximately 3 years. The overall time to receive treatment in this study is approximately 1 year. Based on decision of sponsor, participants with demonstrated clinical benefit can continue treatment beyond 1 year. Participants will make multiple visits to the clinic, and will make a final visit 30 days after receiving their last dose of drug or before the start of subsequent anticancer therapy, whichever occurs first for a follow-up assessment.

Keywords

Neoplasms Lymphoma Drug therapy TAK-981

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Adult male or female participants greater than or equal to (>=)18 years old.
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  3. Population for dose escalation and expansion.
  4. Has histologically confirmed advanced (local regionally recurrent not amenable to curative therapy) or metastatic solid tumors that have no standard therapeutic option with a proven clinical benefit, are intolerant or have refused them, OR
  5. Has relapsed/refractory lymphoma not amenable to therapies with proven clinical benefit or who are intolerant or who refuse them. Participants with low grade lymphomas such as follicular lymphoma, small lymphocytic lymphoma, lymphoplasmacytoid lymphoma, and marginal zone lymphomas, may not need to exhaust all available therapy. These participants can be enrolled after failure of at least 2 prior systemic therapies, provided that there is not an immediate need for cytoreduction. In these cases, participants who need immediate therapy for tumor bulk are not eligible for this trial.
  6. If enrolled before a dose level for which there is consistent evidence of TAK-981 pharmacodynamic effect (DLx) will not be required to have measurable disease. But once that DLx is determined, participants enrolling in dose escalation and expansion cohorts will be required to have measurable disease per RECIST version 1.1 for participants with solid tumors or RECIL 2017 for participants with lymphoma.
  7. Screening and post-dose tumor biopsies are required from all participants in the expansion cohorts and are optional during dose escalation, however once a DLx is identified at which there is clear evidence of TAK-981 biological effect (that is, observation of peripheral lymphopenia, induction of cytokines/chemokines, type 1 interferon (IFN) signature in blood, drug-related toxicity or antitumor effect), subsequent participants must agree in providing a fresh tumor biopsy during the screening period and a second tumor biopsy as requested in the schedule of events (SOE). The lesion accessible for biopsy may not be the only target lesion and should not be located in a previously irradiated field (unless this index lesion has progressive disease >=20% post radiation). Ideally, the same lesion should be biopsied before treatment and on treatment whenever possible.
  8. Adequate bone marrow reserve and renal and hepatic function.
  9. Recovered to Grade 1, baseline or established as sequela, from all toxic effects of previous therapy (except alopecia, neuropathy, or autoimmune endocrinopathies with stable endocrine replacement therapy).
  10. Left ventricular ejection fraction (LVEF) >=40 percent (%); as measured by echocardiogram or multiple gated acquisition scan (MUGA).
  11. Consented to undergo serial skin punch biopsies unless the sponsor decided that there are already enough biopsies for proper target engagement assessment.
  12. . Suitable venous access for safe drug administration and the study-required PK and pharmacodynamics sampling.
  13. . Women of child-bearing potential participating in this study should avoid becoming pregnant, and male participants should avoid impregnating a female partner. Nonsterilized female participants of reproductive age and male participants should use effective methods of contraception through defined periods during and after study treatment as specified below. Female participants must meet 1 of the following:
  14. Postmenopausal for at least 1 year before the screening visit, or
  15. Surgically sterile, or
  16. If they are of childbearing potential, agree to practice 1 highly effective method and 1additional effective (barrier) method of contraception at the same time, from the time of signing of the informed consent form (ICF) through 90 days after the last dose of study drug (whichever is longer), or
  17. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
  18. . Male participants, even if surgically sterilized (that is, status postvasectomy) must agree to 1 of the following:
  19. Agree to practice effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, or
  20. Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)

You CAN'T join if...

  1. Treatment with systemic anticancer treatments or investigational products within 14 days before the first dose of study drug or 5 half-lives, whichever is shorter.
  2. History of uncontrolled brain metastasis.
  3. Is receiving any live vaccine (example, varicella, pneumococcus) within 4 weeks of initiation of study treatment.
  4. Has received extended field radiotherapy less than or equal to (<=) 4 weeks before the start of treatment (<=2 weeks for limited field radiation for palliation), and who has not recovered to grade 1 or better from related side effects of such therapy (except for alopecia).
  5. History of any of the following <=6 months before first dose: congestive heart failure New York Heart Association Grade III or IV, unstable angina, myocardial infarction, unstable symptomatic ischemic heart disease, uncontrolled hypertension despite appropriate medical therapy, ongoing symptomatic cardiac arrhythmias of >Grade 2, pulmonary embolism, or symptomatic cerebrovascular events, or any other serious cardiac condition.
  6. Baseline prolongation of the corrected QT (QTc) interval (example, repeated demonstration of QTc interval >480 milliseconds (ms), history of congenital long QT syndrome, or torsades de pointes).
  7. Psychiatric illness/social circumstances that would limit compliance with study requirements and substantially increase the risk of adverse events (AEs) or has compromised ability to provide written informed consent.
  8. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.
  9. History of autoimmune disease requiring systemic immunosuppressive therapy.
  10. . Active infection.
  11. . Known hepatitis B virus (HBV) surface antigen seropositive or detectable hepatitis C infection viral load. Note: Participants who have positive hepatitis B core antibody or hepatitis B surface antigen antibody can be enrolled but must have an undetectable hepatitis B viral load.
  12. . Known history of human immunodeficiency virus infection or any other relevant congenital or acquired immunodeficiency.
  13. . Receiving or requiring the continued use of medications that are known to be strong or moderate inhibitors and inducers of CYP3A4/5 and strong permeability glycoprotein (P-gp) inhibitors. To participate in this study, such participants should discontinue use of such agents for at least 2 weeks before receiving a dose of TAK-981.
  14. . Lymphomas with leukemic expression.
  15. . Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
  16. . Participants requires the use of drugs known to prolong QTc interval.

Locations

  • University of California San Diego Moores Cancer Center not yet accepting patients
    La Jolla California 92093 United States
  • The University of Texas MD Anderson Cancer Center not yet accepting patients
    Houston Texas 77030 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Millennium Pharmaceuticals, Inc.
ID
NCT03648372
Phase
Phase 1
Study Type
Interventional
Last Updated