A Study of Mobocertinib in Japanese Adults With Non-Small Cell Lung Cancer

NCT03807778 | Active Not Recruiting Phase 1 Results

• 3 other identifiers: TAK-788-1003U1111-1223-2659jRCT2080224519
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 25

Brief Summary

This study is in 2 parts. Different participants will take part in the 1st and 2nd parts of the study. The main aim of the 1st part of the study is to check how much Mobocertinib adults with non-small cell lung cancer (NSCLC) can receive without getting side effects from it. The main aim of the 2nd part of the study is to learn if the condition of adults with non-small cell lung cancer improves after treatment with Mobocertinib. Another aim is to continue checking for side effects from Mobocertinib. In the 1st part of the study, at the first visit, the study doctor will check who can take part. For those that can take part, participants will take a capsule of Mobocertinib once a day for 28 days. This will count as 1 cycle. Different small groups of participants will receive lower to higher doses of Mobocertinib. The study doctors will check for side effects after each dose of TAK 788. In this way, researchers can work out the best dose of Mobocertinib to give participants in the 2nd part of the study. Participants will visit the clinic 30 days after their treatment has finished for a final check-up. In the 2nd part of the study, at the first visit, the study doctor will check who can take part. Participants will receive the best dose of Mobocertinib worked out from the 1st part of the study. Participants will receive Mobocertinib in the same way as those from the 1st part of the study. The study doctors will learn if the condition of these participants improves after treatment with Mobocertinib. The study doctors will also check for side effects from Mobocertinib. After treatment has finished, participants will visit the clinic every 12 weeks until the end of the study. In both parts of the study, participants can receive Mobocertinib for up to just over 1 year, or longer if their condition stays improved.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Phase 1 Part: Recommended Phase 2 Dose (RP2D) of Orally Administered Mobocertinib

  The RP2D was the maximum tolerated dose (MTD) or less. The MTD was declared when at least 9 participants were evaluable in the study and 6 participants were evaluable at the current dose, and the current dose was recommended for the next cohort. The dose recommended for use in phase 2 part was analyzed on the basis of the safety and tolerability data obtained in phase 1 part of the study.

  Cycle 1 (Cycle length=28 days)

• Phase 2 Part: Confirmed Objective Response Rate (ORR) as Assessed by the Independent Review Committee (IRC)

  Confirmed ORR is defined as percentage of participants who were confirmed to had achieved complete response (CR) or partial response (PR) per IRC using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 after the initiation of study treatment. Confirmed responses were responses that persisted on repeat imaging \>=4 weeks after initial response. CR (target lesion response): disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to \<10 millimeter (mm) in short axis. CR (non-target lesion response): disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (\<10 mm short axis) and normalization of tumor marker level. PR (target lesions): at least 30% decrease in sum of the longest diameters (SLD) of target lesions, taking as reference baseline sum diameters. The SLD must also demonstrate an absolute increase of at least 5 mm.

  From the first dose of the study drug until progressive disease (PD) (up to 2 years and 9 months)

Secondary Outcomes (25)

• Phase 1 Part: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  From first dose of study drug until 30 days after the last dose or before initiation of new anticancer therapy (whichever comes first) (Up to 2 years and 9 months, till data cut-off of 08 November 2021)

• Phase 1 Part: Number of Participants With First Cycle DLTs Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.00

  Cycle 1 (Cycle length=28 days)

• Phase 1 Part: Number of DLTs for Mobocertinib Based on NCI CTCAE, Version 5.00

  Cycle 1 (Cycle length=28 days)

• Phase 1 Part: Maximum Tolerated Dose (MTD) of Orally Administered Mobocertinib

  Cycle 1 (Cycle length=28 days)

• Phase 1 Part, Cmax: Maximum Observed Plasma Concentration for Mobocertinib and Its Active Metabolites (AP32960 and AP32914) After a Single Oral Dose

  Cycle 1 Day 1: pre-dose and at 0.5 1, 2, 4, 6, 8 and 24 hours post-dose (Cycle length = 28 days)

Study Arms (2)

Mobocertinib, Phase 1 Part

EXPERIMENTAL

Mobocertinib 40 milligrams (mg) (as the starting dose), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle for up to disease progression or intolerable toxicity, or another discontinuation criterion, and increasing until 160 mg, once daily (for up to approximately 10-12 cycles).

Drug: Mobocertinib

Mobocertinib, Phase 2 Part

EXPERIMENTAL

Mobocertinib 160 mg, once daily, for up to approximately 10-12 cycles.

Drug: Mobocertinib

Interventions

Mobocertinib DRUG

Mobocertinib capsule.

Also known as: TAK-788, AP32788

Mobocertinib, Phase 1 Part; Mobocertinib, Phase 2 Part

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥20 years old.
• Must have measurable disease by RECIST v1.1. Previously irradiated lesions may not be used for target lesions, unless there is unambiguous radiological progression after radiotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
• Minimum life expectancy of 3 months or more.
• Adequate renal and hepatic function as defined by the following criteria:
• Total serum bilirubin ≤1.5 × upper limit of normal (ULN) (≤3.0 × ULN for patients with Gilbert syndrome or if liver function abnormalities are due to underlying malignancy);
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN (or ≤5 × ULN if liver function abnormalities are due to underlying malignancy);
• Estimated creatinine clearance ≥30 mL/min (calculated by using the Cockcroft-Gault equation);
• Serum albumin ≥2 g/dL; and
• Serum lipase ≤1.5 × ULN; and
• Serum amylase ≤1.5 × ULN unless the increased serum amylase is due to salivary isoenzymes.
• Adequate bone marrow function as defined by the following criteria:
• Absolute neutrophil count ≥1.5 × 109/L;
• Platelet count ≥75 × 109/L in Phase 1 Part and ≥100 × 109/L in Phase 2 Part; and
• Hemoglobin ≥9.0 g/dL.

You may not qualify if:

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• Have been diagnosed with another primary malignancy other than NSCLC except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
• Have undergone major surgery within 28 days prior to first dose of Mobocertinib. Minor surgical procedures, such as catheter placement or minimally invasive biopsy, are allowed.
• Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).
• Have significant, uncontrolled, or active cardiovascular disease, including, but not restricted to:
• Myocardial infarction within 6 months prior to the first dose of study drug;
• Unstable angina within 6 months prior to first dose;
• Congestive heart failure within 6 months prior to first dose;
• History of clinically significant (as determined by the treating physician) atrial arrhythmia;
• Any history of ventricular arrhythmia; or
• Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose.
• Have uncontrolled hypertension. Patients with hypertension should be under treatment on study entry to control blood pressure.
• Currently being treated with medications known to be associated with the development of Torsades de Pointes.
• Have an ongoing or active infection, including, but not limited to, the requirement for intravenous antibiotics. Have a known history of HIV infection. Testing of HIV is not required in the absence of history.Hepatitis B surface antigen (HBsAg) positive patients are allowed to enroll if hepatitis B virus (HBV)-DNA is below 1000 copies/mL in the plasma.Patients who have positive hepatitis C virus (HCV) antibody can be enrolled but must have HCV-RNA undetectable in the plasma.
• Currently have or have a history of interstitial lung disease (ILD), radiation pneumonitis that required steroid treatment, or drug-related pneumonitis.

Sponsors & Collaborators

• Takeda: lead

Study Sites (25)

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, Japan

Location

Fujita Health University Hospital

Toyoake, Aichi-ken, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Location

Kurume University Hospital

Kurume, Fukuoka, Japan

Location

Hokkaido Cancer Center

Sapporo, Hokkaido, Japan

Location

Hyogo Cancer Cente

Akashi, Hyōgo, Japan

Location

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, Japan

Location

Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Location

Sendai Kousei Hospital

Sendai, Miyagi, Japan

Location

Okayama University Hospital

Kita-ku, Okayama-ken, Japan

Location

Kansai Medical University Hospital

Hirakata, Osaka, Japan

Location

National Hospital Organization Kinki-Chuo Chest Medical Center

Sakai, Osaka, Japan

Location

Kindai University Hospital

Sayama, Osaka, Japan

Location

Saitama Cancer Center

Shinden, Saitama, Japan

Location

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

Bunkyo-ku, Tokyo, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Location

Cancer Institute Hospital

Koto-ku, Tokyo, Japan

Location

Yamaguchi Ube Medical Center

Ube, Yamaguchi, Japan

Location

Kyushu University Hospital

Fukuoka, Japan

Location

Hiroshima University Hospital

Hiroshima, Japan

Location

Kyoto University Hospital

Kyoto, Japan

Location

Niigata Cancer Center Hospital

Niigata, Japan

Location

Osaka International Cancer Institute

Osaka, Japan

Location

Tokushima University Hospital

Tokushima, Japan

Location

Wakayama Medical University Hospital

Wakayama, Japan

Location

Related Publications (1)

• Yang JC, Zhou C, Janne PA, Ramalingam SS, Kim TM, Riely GJ, Spira AI, Piotrowska Z, Mekhail T, Garcia Campelo MR, Felip E, Bazhenova L, Jin S, Kaur M, Diderichsen PM, Gupta N, Bunn V, Lin J, N Churchill E, Mehta M, Nguyen D. Characterization and management of adverse events observed with mobocertinib (TAK-788) treatment for EGFR exon 20 insertion-positive non-small cell lung cancer. Expert Rev Anticancer Ther. 2023 Jan;23(1):95-106. doi: 10.1080/14737140.2023.2157815. Epub 2022 Dec 28.

  PMID: 36537204 DERIVED

Related Links

• To obtain more information on the study, click here/on this link

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

mobocertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  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: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2019
• First Posted: January 17, 2019
• Study Start: February 4, 2019
• Primary Completion: November 8, 2021
• Study Completion (Estimated): September 30, 2026
• Last Updated: May 14, 2026
• Results First Posted: October 3, 2023

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

JP (25)