A phase 1 study of TAS0728 in patients with advanced solid tumors with HER2 aberration

JRCT ID: jRCT2031240235

Registered date:24/07/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: solid tumors with HER2 aberrations
• Date of first enrollment: 01/08/2024
• Target sample size: 30
• Study type: Interventional

Intervention(s)

-Dose escalation part
TAS0728 50 mg (dose level 1) will be the starting dose for study intervention. After the safety of each level is confirmed by the 3+3 design, the patient will be moved to the next level. Repeat twice daily for 21 consecutive days.
Level 1: 50 mg BID
Level 2: 75 mg BID
Level 3: 100 mg BID

-Dose expansion part
Each cohort will be treated at the recommended dose determined in the dose escalation part. Dose should be taken twice daily for 21 consecutive days for one cycle.

Outcome(s)

Primary Outcome

Dose escalation part
-Dose Limiting Toxicity

Dose expansion part
- Adverse event

Secondary Outcome

Dose escalation part
- Pharmacokinetics
- Adverse event
- Best Response
- Progression-free survival period
- Duration of response
- Overall response (CR+PR)
- Disease control (CR+PR+SD)

Dose expansion part
- Pharmacokinetics
- Best Response
- Progression-free survival period
- Duration of response
- Overall response (CR+PR)
- Disease control (CR+PR+SD)

Key inclusion & exclusion criteria

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

Include criteria

1. Patients who are at least 18 years of age at the time of signing the Informed Consent Form (ICF)
2. Patients who are diagnosed with a histologically unresectable solid tumor that has received or cannot receive standard treatment
3. Has met one of the following criteria for genetic testing:
a. Has a HER2 mutation if diagnosed with lung cancer;
b. If diagnosed with a solid tumor other than lung cancer, one of the following;
i. HER2 immunostaining (IHC) 3+
ii. HER2 immunostaining (IHC) 2+ and ISH positive for HER2
iii. HER2 gene mutation
4. Evaluable lesions on CT or MRI (measurable lesions are not required)
5. ECOG performance status of 0 to 1.
6. Has the following laboratory values on examination within 7 days prior to treatment with the investigational drug
a. Neutrophil count >= 1.5 x 10^9/L (1,500/microL)
b. Hemoglobin >= 8.0 g/dL
c. Platelet count >= 75 x 10^9/L (75,000/microL)
d. Albumin >= 3 g/dL
e. Serum potassium, magnesium, phosphorus, sodium, and total calcium levels within institutional reference values
f. AST and ALT <= 3.0 x ULN (<= 5.0 x ULN if liver function is abnormal due to liver metastases)
g. Serum total bilirubin <= 1.5 x ULN
h. Serum creatinine <= 1.4 x ULN or creatinine clearance (CrCl) >= 50 mL/min
i. For calculated values, CrCl is calculated using the following Cockcroft-Gault equation
ii. CrCl for men = (140 - age) x weight [kg] / [72 x serum creatinine (mg/dL)
iii. CrCl for women = CrCl for men x 0.85
iv. If urine is stored for 24 hours, use the measured value.
7. Corrected QT using Fridericia formula (QTcF) < 450 ms (< 470 ms for women)
8. Left ventricular ejection fraction (LVEF) on echocardiography or multigate scan (MUGA) > the lower limit of the institutional reference value (> 50% if no institutional reference value)
9. Negative for hepatitis B virus surface (HBs) antigen and HBs antibody or hepatitis B virus core (HBc) antibody (however, patients who are HBs or HBc antibody positive and hepatitis B virus [HBV] DNA negative may be registered)
10. Negative for hepatitis C virus (HCV) antibodies (however, patients who are positive for HCV antibodies and negative for HCV RNA may be enrolled)
11. Recovery of previously treated side effects (except alopecia, hyperpigmentation, and anemia) to Grade 1 or less
12. Patients who are eligible for oral administration of drugs
13. Expected to survive more than 12 weeks
14. Male and/or female
15. Capable of giving signed informed consent as described in the informed consent form and in the protocol.

Exclude criteria

1. Any of the following cardiac dysfunction or clinically significant cardiac disease
a. Symptomatic chronic heart failure (NYHA classes II-IV) or previous or concurrent arrhythmia requiring treatment
b. Previous or concurrent myocardial infarction or angina pectoris
c. Uncontrolled hypertension
d. Clinically significant valvular heart disease
e. Suspected or previous/complicated Brugada syndrome
f. Conditions that may result in drug-induced QT prolongation
i. Congenital or acquired QT prolongation syndrome
ii. Family history of sudden death
iii. History of drug-induced
iv. Concomitant use of medications associated with QT prolongation (e.g., imipramine, mozide, quinidine, procainamide, disopyramide)
2. Any of the following treatment within the defined time period prior to the investigational drug administration.
a. Extensive surgery within 4 weeks (28 days) prior to study drug administration (surgical wounds must have completely healed prior to the first dose of study drug)
b. Extensive radiation therapy within 4 weeks prior to study drug administration or local radiation therapy within 2 weeks prior to first dose of study drug
c. Local treatment within 4 weeks prior to study drug administration [transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT), or ablation, etc.]
d. Anticancer therapy within 2 weeks (14 days) prior to study drug administration (within the past 5 weeks for mitomycin). molecular-targeted agents or immunotherapy, not more than 2 weeks or 5 times the half-life (whichever is shorter)
e. Other investigational agents being administered or within 3 weeks prior to administration of the investigational agent in this study
3. Has any clinically significant acute or chronic medical or psychiatric condition of any clinical significance that may increase the risk associated with the administration of the investigational drug or that may affect the interpretation of study results, or any laboratory abnormalities, including but not limited to
a. Brain metastases (not including primary brain tumors) that have not been clinically stable for at least 2 months after steroid withdrawal
b. Soft tissue metastases
c. Acute systemic infection
d. Diarrhea or vomiting regardless of severity
e. Moderate or greater nausea
f. Severe chronic renal disease
g. A history of interstitial lung disease requiring steroid therapy or complications of such disease
h. Liver disease, including non-compensated liver disease
i. Life-threatening autoimmune disease
j. Other severe acute or chronic medical symptoms or mental status or laboratory abnormalities that, in the judgment of the investigator, would make the subject ineligible for enrollment in this study
4. Chronic pulmonary dysfunction or pleural effusion (malignant or benign) requiring chronic oxygen therapy
5. Poorly controlled pleural effusion or ascites.
6. Has a serious gastrointestinal disorder that may cause gastrointestinal perforation
7. Has a gastrointestinal disorder that may affect absorption of oral drugs, or has undergone surgery or treatment of the gastrointestinal system
Other exclusion criteria
8. judged by the investigator to be unsuitable as a patient for this study
9. Pregnant or lactating patient. However, if lactation is discontinued ( not resumed), the patient can be enrolled.
10. Lung cancer patients with a history of prior HER2 tyrosine kinase inhibitor treatment in the dose escalation part (participation in the dose escalation part is not excluded)
11. Patients with a history of hypersensitivity to any component of the investigational drug
12. Patients requiring continuation of strong CYP3A inhibitor or inducer

Related Information

• Primary Sponsor: Tsurutani Junji
• Source(s) of Monetary Support: Taiho Pharmaceutical Co., Ltd.