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

NCT02834247 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: C340032016-000853-10U1111-1181-8312
• Study Type: interventional
• Target: 41
• Locations: 4 countries
• Sites: 22

Brief Summary

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.

Conditions

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

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (3)

• Part 1, Dose Escalation Phase: Maximum Tolerated Dose (MTD)

  The MTD was defined as the dose range at which less than or equal to (\<=) 1 of 6 evaluable participants experience dose limiting toxicities (DLT) within the first 28 days of treatment (end of Cycle 1). Toxicities were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.

  At end of Cycle 1 Day 28

• Part 1, Dose Escalation Phase: Recommendation Phase 2 Dose (RP2D)

  RP2D was evaluated from cumulative toxicities in Cycle 1 and beyond. Toxicities were evaluated according to NCI CTCAE version 4.03.

  Up to Cycle 12 (each Cycle length is equal to [=] 28 days)

• Part 2, Dose Expansion Phase: Overall Response Rate (ORR)

  ORR was defined as the percentage of participants who's best overall response (BOR) was either complete response (CR) or partial response (PR). The ORR assessment was based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The BOR was defined as the best response recorded from the start of the study treatment until the start of subsequent anticancer therapy. CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (\<) 10 millimeter (mm). PR: was at least a 30 percent (%) decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD.

  From the start of study treatment until the start of subsequent anticancer therapy (up to 28 months)

Secondary Outcomes (9)

• Percentage of Participants Who Experienced at Least One Treatment-emergent Adverse Events (TEAEs), Grade 3 or 4 Adverse Events (AEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation

  From the first dose of the study drug up to 28 days after the last dose of the study drug or the start of subsequent anticancer therapy (up to 28 months)

• Part 2, Dose Expansion Phase: Disease Control Rate (DCR)

  From the start of study treatment until the start of subsequent anticancer therapy (up to 28 months)

• Part 2, Dose Expansion Phase: Duration of Response (DOR)

  From the date of first documentation of a response to the date of first documented PD (up to 28 months)

• Part 2, Dose Expansion Phase: Percentage of Participants With PD at Month 6

  Month 6

• Part 2, Dose Expansion Phase: Progression Free Survival (PFS)

  From the date of first study drug administration up to date of first documented PD or death due to any cause, whichever occurred first (up to 28 months)

Study Arms (5)

Part 1: Advanced Solid Tumors

EXPERIMENTAL

TAK-659 60 milligram (mg), tablets, orally, once daily in each 28-day treatment cycle in combination with nivolumab 3 milligram per kilogram (mg/kg), infusion over 60 minutes, intravenously (IV), on Days 1 and 15 in each 28 day treatment cycle until PD or unacceptable toxicity. Dose escalation of TAK-659 to 100 mg may be done using a 3 + 3 dose escalation design to determine a maximum tolerated dose (MTD) and/or RP2D.

Drug: TAK-659; Drug: Nivolumab

Nivolumab Fixed Dose Cohort

EXPERIMENTAL

After RP2D of TAK-659 has been identified, based on evaluation of combination with weight-based dose of nivolumab (3 mg/kg), RP2D may be evaluated in combination with a fixed dose of 240 mg IV nivolumab after discussion between investigator and sponsor for all types of advanced solid tumors. For single-agent nivolumab, fixed dose is expected to have equal exposure, safety, and efficacy as weight-based (3 mg/kg) dose. If nivolumab fixed dose is evaluated with TAK-659 RP2D, 3 participants will be initially enrolled into cohort. Following evaluation of safety, efficacy, and any available PK data, along with discussions between investigator and sponsor, 3 additional participants may be enrolled into cohort for a total of 3 to 6 participants. If \>=1 out of 6 participants experiences dose-limiting toxicity (DLT) in Cycle 1, or significant safety issues are seen in Cycle 2 and beyond, re-evaluation of TAK-659 RP2D when administered with a fixed dose of nivolumab is permitted.

Drug: TAK-659; Drug: Nivolumab

Part 2: Metastatic Triple-negative Breast Cancer (TNBC)

EXPERIMENTAL

Participants with metastatic TNBC will receive TAK-659 at the RP2D as determined in Part 1, tablets, orally, once daily in each 28-day treatment cycle in combination with nivolumab 3 mg/kg, infusion over 60 minutes, intravenously, on Day 1 and Day 15 of each 28 day treatment cycle until PD or unacceptable toxicity. A subset of participants will receive two weeks of TAK-659 monotherapy during Cycle 1, and will receive nivolumab beginning on Day 15 of Cycle 1. The dose of nivolumab will be either 3 mg/kg or 240 mg IV, dependent on whether the 240 mg fixed-dose cohort is evaluated and deemed safe and tolerable. If so, the dosing regimen may switch to 240 mg, on the basis of change in clinical practice and discussion between the investigator and sponsor. If the nivolumab fixed-dose evaluation cohort is not run, the dose of nivolumab for all participants in the dose expansion phase will be 3 mg/kg.

Drug: TAK-659; Drug: Nivolumab

Part 2: Metastatic Non-small Cell Lung Cancer (NSCLC)

EXPERIMENTAL

Participants with metastatic NSCLC will receive TAK-659 at the RP2D as determined in Part 1, tablets, orally, once daily in each 28-day treatment cycle in combination with nivolumab 3 mg/kg, infusion over 60 minutes, intravenously, on Day 1 and Day 15 of each 28 day treatment cycle until PD or unacceptable toxicity. A subset of participants will receive two weeks of TAK-659 monotherapy during Cycle 1, and will receive nivolumab beginning on Day 15 of Cycle 1.disease or unacceptable toxicity. The dose of nivolumab will be either 3 mg/kg or 240 mg IV, dependent on whether the 240 mg fixed-dose cohort is evaluated and deemed safe and tolerable. If so, the dosing regimen may switch to 240 mg, on the basis of change in clinical practice and discussion between the investigator and sponsor. If the nivolumab fixed-dose evaluation cohort is not run, the dose of nivolumab for all participants in the dose expansion phase will be 3 mg/kg.

Drug: TAK-659; Drug: Nivolumab

Part 2: Metastatic HNSCC

EXPERIMENTAL

Participants with Head and Neck Squamous Cell Carcinoma (HNSCC) will receive TAK-659 at the RP2D as determined in Part 1, tablets, orally, once daily in each 28-day treatment cycle in combination with nivolumab 3 mg/kg, infusion over 60 minutes, intravenously, on Day 1 and Day 15 of each 28 day treatment cycle until PD or unacceptable toxicity. A subset of participants will receive two weeks of TAK-659 monotherapy during Cycle 1, and will receive nivolumab beginning on Day 15 of Cycle 1. The dose of nivolumab will be either 3 mg/kg or 240 mg IV, dependent on whether the 240 mg fixed-dose cohort is evaluated and deemed safe and tolerable. If so, the dosing regimen may switch to 240 mg, on the basis of change in clinical practice and discussion between the investigator and sponsor. If the nivolumab fixed-dose evaluation cohort is not run, the dose of nivolumab for all participants in the dose expansion phase will be 3 mg/kg.

Drug: TAK-659; Drug: Nivolumab

Interventions

TAK-659 DRUG

TAK-659 Tablets.

Nivolumab Fixed Dose Cohort; Part 1: Advanced Solid Tumors; Part 2: Metastatic HNSCC; Part 2: Metastatic Non-small Cell Lung Cancer (NSCLC); Part 2: Metastatic Triple-negative Breast Cancer (TNBC)

Nivolumab DRUG

Nivolumab intravenous infusion.

Nivolumab Fixed Dose Cohort; Part 1: Advanced Solid Tumors; Part 2: Metastatic HNSCC; Part 2: Metastatic Non-small Cell Lung Cancer (NSCLC); Part 2: Metastatic Triple-negative Breast Cancer (TNBC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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.

Sponsors & Collaborators

• Calithera Biosciences, Inc: lead

Study Sites (22)

UCSD

La Jolla, California, 92093, United States

Location

Emory

Atlanta, Georgia, 30322, United States

Location

Massachusetts General

Boston, Massachusetts, 2114, United States

Location

Barbara Ann Karmanos

Detroit, Michigan, 48201, United States

Location

Roswell Park

Buffalo, New York, 14263, United States

Location

Fox Chase

Philadelphia, Pennsylvania, 19111, United States

Location

Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Mary Crowley Research Centers

Dallas, Texas, 75002, United States

Location

US Oncology

Fairfax, Virginia, 22031, United States

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) S.r.l

Meldola, 47014, Italy

Location

Istituto di Ricovero e Cura a Carattere Scientifico - Istituto Clinico Humanitas (Humanitas Research

Milan, 20089, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Azienda Ospedaliero - Universitaria di Modena Policlinico

Modena, 41124, Italy

Location

Azienda Ospedaliera Universitaria Senese - Policlinico Santa Maria Alle Scotte

Siena, 53100, Italy

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Consejo Superior de Investigaciones Cientificas (CSIC) - Centro de Investigacion del Cancer (CIC)

Salamanca, 37007, Spain

Location

Hospital Universitario La Fe

Valencia, 46009, Spain

Location

Hospital Clinico Universitario de Valencia (CHUV)

Valencia, 46010, Spain

Location

The Newcastle upon Tyne Hospitals NHS Foundation Trust - Freeman Hospital - Northern Centre for Canc

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust - Southampton General Hospital

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• Juric D, Barve M, Vaishampayan U, Roda D, Calvo A, Janez NM, Trigo J, Greystoke A, Harvey RD, Olszanski AJ, Opyrchal M, Spira A, Thistlethwaite F, Jimenez B, Sappal JH, Kannan K, Riley J, Li C, Li C, Gregory RC, Miao H, Wang S. A phase Ib study evaluating the recommended phase II dose, safety, tolerability, and efficacy of mivavotinib in combination with nivolumab in advanced solid tumors. Cancer Med. 2024 Mar;13(5):10.1002/cam4.6776. doi: 10.1002/cam4.6776.

  PMID: 38501219 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck

Interventions

TAK-659; Nivolumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director Clinical Science

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2016
• First Posted: July 15, 2016
• Study Start: August 12, 2016
• Primary Completion: November 30, 2018
• Study Completion: November 30, 2018
• Last Updated: February 8, 2023
• Results First Posted: March 31, 2020

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

US (9); ES (6); GB (2); IT (5)