A Study of TAK-659 in Combination With Nivolumab in Participants With Advanced Solid Tumors

Stopped early · Phase 1

Conditions studied: Triple-Negative Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Head and Neck Carcinoma, Squamous Cell, Advanced Solid Tumors

In brief

The purpose of this study is to evaluate the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D), safety and efficacy of TAK-659 in combination with nivolumab in participants with advanced solid tumors.

Key facts

Study ID

NCT02834247

Run by

Calithera Biosciences, Inc

People needed

41

Starts

2016-08-12

Expected to finish

2018-11-30

Last updated by the study team

2023-02-08

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Is a male or female participant aged 18 years or older.
• Has eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Female participants who:
• Are postmenopausal for at least 1 year before the Screening visit, or
• Are surgically sterile, or
• If childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 180 days after the last dose of study drug, or
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participants. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
• Male participants, even if surgically sterilized (that is, status postvasectomy), who:
• Agree to practice effective barrier contraception during the entire study treatment period and through 180 days after the last dose of study drug, or
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participants. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
• Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participants at any time without prejudice to future medical care.
• Suitable venous access for the study-required blood sampling, including PK and pharmacodynamic (PD) sampling.
• Clinical laboratory values and other measures as specified below within 28 days before the first dose of study drug:
• Total bilirubin must be <=1.5*the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be <=2.5*ULN.
• Creatinine clearance must be greater than or equal to (>=) 60 milliliter per (mL/) minute as estimated by the Cockcroft Gault equation or based on urine collection (12 or 24 hours).
• Hemoglobin must be >=8 gram per deciliter (g/dL), absolute neutrophil count (ANC) must be >=1500 per microliter (/mcL), and platelet count must be >=75,000/mcL.
• Lipase must be <=1.5*ULN and amylase <=1.5*ULN with no clinical symptoms suggestive of pancreatitis and cholecystitis.
• Blood pressure <=Grade 1 (hypertensive participants are permitted if their blood pressure is controlled to <=Grade 1 by hypotensive medications and glycosylated HbA1C <=6.5%).
• Recovered (that is, <=Grade 1 toxicity) from the reversible effects of prior anticancer therapy.
• To be enrolled in the dose escalation phase of the study, participants must have a radiographically or clinically evaluable tumor, but measurable disease as defined by RECIST version 1.1 is not required for participation in this study.
• To be enrolled in the TNBC expansion cohort, participants must have:
• Histologically confirmed, metastatic TNBC with measurable disease per RECIST version 1.1.
• Triple-negative disease (estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) negativity confirmed on a histological biopsy of a metastatic tumor lesion (receptor conversion not allowed).
• Safely accessible tumor lesions (based on investigator's assessment) for serial pre treatment and post treatment biopsies are required for participants receiving TAK-659 monotherapy run-in treatment for 2 weeks followed by TAK-659 plus nivolumab combination treatment [ approximately 10/30 response-evaluable participants]; adequate, newly obtained, core or excisional biopsy of a metastatic tumor lesion not previously irradiated is required. Mandatory biopsies will be taken before TAK-659 monotherapy, after the 2 weeks of TAK-659 monotherapy, and after 6 weeks of TAK-659 plus nivolumab combination therapy. An optional biopsy may be taken at PD with additional consent from the participants.

You may not qualify if…

• Has active brain metastases or leptomeningeal metastases.
• Has active, or suspected autoimmune disease or a history of known autoimmune disease, with the exception of:
• o Participants with vitiligo, type I diabetes mellitus, resolved childhood asthma/atopy, residual hypothyroidism due to autoimmune condition requiring only hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Any condition requiring systemic treatment with corticosteroids (less than [>]10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 before first dose of study drug.
• o Corticosteroids for topical use or in nasal spray are allowed, as are inhaled steroids and adrenal replacement steroid doses >10 mg daily in the absence of active autoimmune disease.
• Has history of pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on the Screening chest computed tomography scan (CT scan); history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Has history of interstitial lung disease.
• Prior therapy with experimental antitumor vaccines; any T-cell co-stimulation agents or inhibitors of checkpoint pathways, such as anti- programmed cell death protein 1 (PD-1), anti- programmed cell death 1 ligand 1 (PD-L1), anti- programmed cell death 1 ligand 2 (PD-L2), anti-CD137, or anti-CTLA-4 antibody; or other agents specifically targeting T cells are prohibited. However, for dose escalation, prior treatment with the marketed inhibitors of the immune checkpoint pathway, such as nivolumab and pembrolizumab, is allowed. In addition, in each of the expansion cohorts, 6 response-evaluable participants with prior exposure to anti-PD-1 or anti-PD-L1 agents will be allowed to enroll.
• Has any serious medical or psychiatric illness, including drug or alcohol abuse, that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Has life-threatening illness unrelated to cancer.
• Is female participant who are lactating and breast-feeding or a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug.
• Systemic anticancer treatment including investigational agents or radiotherapy <2 weeks before the first dose of study treatment (<4 weeks for antibody-based therapy including unconjugated antibody, antibody-drug conjugate, and bi-specific T-cell engager agents; <=8 weeks for cell-based therapy or antitumor vaccine) or have not recovered from acute toxic effects from prior chemotherapy and radiotherapy.
• Prior treatment with investigational agents =<21 days or =<5*their half-lives (whichever is shorter) before the first dose of study treatment. A minimum of 10 days should elapse from prior therapy to initiating protocol therapy.
• Major surgery within 14 days before the first dose of study drug and not recovered fully from any complications from surgery.
• Systemic infection requiring intravenous antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
• Known human immunodeficiency virus (HIV) positive (testing not required).
• Known hepatitis B surface antigen-positive or known or suspected active hepatitis C infection (testing not required).
• Participants with another malignancy within 2 years of study start. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection and are considered disease-free at the time of study entry.
• Any clinically significant comorbidities, such as uncontrolled pulmonary disease, known impaired cardiac function or clinically significant cardiac disease (specified below), active central nervous system disease, active infection, or any other condition that could compromise the participant's participation in the study.
• Participants with any of the following cardiovascular conditions are excluded:
• Acute myocardial infarction within 6 months before starting study drug.
• Current or history of New York Heart Association Class III or IV heart failure
• Evidence of current uncontrolled cardiovascular conditions including cardiac arrhythmias, angina, pulmonary hypertension, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Fridericia corrected QT interval (QTcF) >450 milliseconds (msec) (men) or >475 msec (women) on a 12-lead electrocardiogram (ECG) during the Screening period.
• Abnormalities on 12-lead ECG including, but not limited to, changes in rhythm and intervals that in the opinion of the investigator are considered to be clinically significant.

Where it is running

• UCSD — La Jolla, California, United States
• Emory — Atlanta, Georgia, United States
• Massachusetts General — Boston, Massachusetts, United States
• Barbara Ann Karmanos — Detroit, Michigan, United States
• Roswell Park — Buffalo, New York, United States
• Fox Chase — Philadelphia, Pennsylvania, United States
• Vanderbilt — Nashville, Tennessee, United States
• Mary Crowley Research Centers — Dallas, Texas, United States
• US Oncology — Fairfax, Virginia, United States
• Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) S.r.l — Meldola, Italy
• Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Clinico Humanitas (Humanitas Research — Milan, Italy
• Ospedale San Raffaele — Milan, Italy
• Azienda Ospedaliero - Universitaria di Modena Policlinico — Modena, Italy
• Azienda Ospedaliera Universitaria Senese - Policlinico Santa Maria Alle Scotte — Siena, Italy
• Hospital General Universitario Gregorio Maranon — Madrid, Spain
• Hospital Universitario Ramon y Cajal — Madrid, Spain
• Hospital Clinico Universitario Virgen de la Victoria — Málaga, Spain
• Consejo Superior de Investigaciones Cientificas (CSIC) - Centro de Investigacion del Cancer (CIC) — Salamanca, Spain
• Hospital Universitario La Fe — Valencia, Spain
• Hospital Clinico Universitario de Valencia (CHUV) — Valencia, Spain
• The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital - Northern Centre for Canc — Newcastle upon Tyne, United Kingdom
• University Hospital Southampton NHS Foundation Trust - Southampton General Hospital — Southampton, United Kingdom

Full record on ClinicalTrials.gov

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