Phase Ia/Ib Basket Trial on the safety and efficacy of Mobocertinib in combination with T-DM1 for patients with HER2 mutant solid tumors (WJOG16022M)

JRCT ID: jRCT2051220070

Registered date:08/08/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Solid tumor
• Date of first enrollment: 01/11/2022
• Target sample size: 38
• Study type: Interventional

Intervention(s)

Phase Ia part:
Mobocertinib is administered with 80 mg QD as an initial dose and then adjusted between 80, 120 and 160 mg QD based on "3 + 3" design. The dose of T-DM1 is fixed at 3.6 mg/kg every three weeks.
Phase Ib part:
The dose of Mobocertinib is a recommended dose (RD) determined in Phase Ia part. The dose of T-DM1 is fixed at 3.6 mg/kg every three weeks.

Outcome(s)

• Primary Outcome: Objective response rate by investigators' assessment
• Secondary Outcome: Disease control rate, Overall survival, Progression-free survival, Duration of response, Time to response, Time to treatment failure, and Safety

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) 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of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
2) Male or female adult patients 18 years or older.
3) Patients with a histologically confirmed diagnosis of advanced or recurrent solid tumors (including sarcoma)
4) Patients with advanced or recurrent solid tumors that have become refractory to standard therapies, or have no satisfactory standard therapy
5) Patients with a history of most recent systemic therapies for advanced or recurrent solid tumors or subsequent disease progression.
6) Patients with solid tumors positive for HER2 activating mutations. (Not required for Phase Ia part, but required for Phase Ib part).
7) Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines version 1.1 (Not required for Phase Ia part, but required for Phase Ib part).
8) Patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
9) Life expectancy >= 3 months
10) Patients who are able to receive oral administration (e.g., do not require tube feeding)
11) Patients with adequate organ function
12) Left ventricular ejection fraction (LVEF) >=50% as assessed by echocardiogram or multi-gated acquisition scan (MUGA).
13) Normal QT interval on screening ECG evaluation, defined as QT interval corrected (Fridericia) (QTcF) of <=450 milliseconds in males or <=470 milliseconds in females.

Exclude criteria

1) Previous treatment with HER2-directed therapy (Not required for Phase Ia part, but required for Phase Ib part)
2) Have symptomatic brain metastasis.
3) Patients with meningeal dissemination
4) Have significant, uncontrolled, or active cardiovascular disease.
5) Currently being treated with medications known to be associated with the development of torsade de pointes.
6) Have a history or the presence at baseline of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis that required steroid treatment.
7) Have malabsorption syndrome or other gastrointestinal (GI) illness that could affect swallowing and/or oral absorption of mobocertinib.
8) Patients who had undergone prior treatment (chemotherapy, molecular-targeted therapy, antibody therapy, hormone therapy, immunotherapy, radiotherapy) within 2 weeks prior to study enrollment
9) Patients who have multiple cancers.
10) Patients who have tested positive for hepatitis B virus or hepatitis C virus and are suspected of acute or chronic infection.
11) Have a known history of HIV infection. Testing is not required in the absence of history.
12) Female patients who are both 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
13) Received systemic treatment with moderate or strong cytochrome p-450 (CYP)3A inhibitor or moderate or strong CYP3A inducer within 14 days before enrollment.
14) Patients who have a concurrent or previous history of severe hypersensitivity to other drugs including antibody products.
15) Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
16) Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the evaluation of mobocertinib and T-DM1.
17) Patients with other medically significant abnormalities

Related Information

• Primary Sponsor: Hidetoshi Hayashi
• Source(s) of Monetary Support: Takeda Pharmaceutical Company Limited
• Secondary ID(s): Nil known