Study of Dosage Exploration and Pharmacokinetics for HA121-28 Tablets

Phase 1

• Conditions: Advanced Solid Tumor
• Interventions: Drug: HA121-28 tablets

• Registration Number: NCT03994484
• Lead Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Brief Summary

There are 2 phases in this study: Phase 1 (dose escalation) and Phase 2 (dose expansion).

The goal of Phase 1 of this clinical research study is to find the highest tolerable dose of HA121-28 tablets that can be given to patients with advanced cancer. The goal of Phase 2 of this study is to learn if the dose of HA121-28 tablets found in Phase 1 can help to control advanced cancer.

The safety of HA121-28 tablets will be studied in both phases of the study.

Detailed Description

If participants are found to be eligible to take part in this study, they will be assigned to a study group based on when they join this study. Up to 8 groups of up to 20 participants will be enrolled in Phase 1 of the study, and up to 3 groups of up to 24 participants will be enrolled in Phase 2.

If participant is enrolled in Phase 1, the dose of HA121-28 tablets they receive will depend on when they join this study. The first group of participants will receive the lowest dose level of HA121-28 tablets. Each new group will receive a higher dose of HA121-28 tablets than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of HA121-28 tablets is found. If participant is enrolled in Phase 2, they will receive HA121-28 tablets at the low, medium and high doses to select the recommended dose for phase Ⅱ clinical trials.

Study Timeline

• Study Start: 2018-10-10
• Study First Submitted: 2019-06-18
• Study First Submitted QC: 2019-06-19
• Study First Posted: 2019-06-21
• Status Verified: 2022-02
• Last Update Submitted: 2022-02-08
• Last Update Posted: 2022-02-10
• Primary Completion: 2022-12-30
• Study Completion: 2022-12-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

1. Be willing to participate in the clinical trial and sign the informed consent;

2. Men and women aged 18 to 75 years;

3. Histologically/cytologically confirmed advanced/metastatic solid tumor, and have failed prior standard therapy or for which no standard therapy is durable(patients with RET fusion/mutation can be included regardless of whether they have received standard therapy or not);

4. At least one measurable lesion according to RECIST 1.1 ;

5. Subject has not received any anti-cancer therapies including chemotherapy, radiotherapy, targeted treatment and surgery within 4 weeks prior to participation;

6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0~1;

7. Expected overall survival (Life expectancy)≥ 3 months;

8. Laboratory test results must meet the following standards:

   Absolute neutrophil count (ANC) ≥1.5 x 10^9/L; Platelet count (PLT) ≥75×10^9/L; Hemoglobin (Hb) ≥90 g/L (no blood transfusion within 14 days); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN) (in patients with liver metastasis ≤5.0 x ULN); Total bilirubin ≤ 1.5 x ULN; Serum creatinine≤ 1.5 x ULN；

9. Male and female subjects of childbearing potential should agree to use suitable method of contraception during the treatment and 6 months after the last dose of study medication; female participants should have negative results of serum/urine pregnancy test within 7 days prior to enrollment and cannot be breastfeeding.

Exclusion Criteria

1. Has participated in other clinical trials and received the treatment within 4 weeks prior to enrollment;

2. Patients who cannot swallow or have chronic diarrhea and intestinal obstruction, which may affect the administration and absorption of the drug;

3. Subject who meets one of the following criteria:

   • Corrected QT (QTc) ≥470ms in women, ≥450ms in men; or congenital long QT syndrome (LQTS), taking QT prolonging medications, and has a family history of long QT syndrome;
   • Resting ECG result shows clinically significant abnormalities of rhythm, conduction or morphology, requiring therapeutic intervention;

4. Urinalysis result shows protein in urine ≥ ++ and 24-hour urine protein > 1.0g;

5. Based on the investigator's assessment, patients with known severe comorbidities which may influence the safety of the patients and the study completion [such as uncontrolled hypertension (systolic pressure ≥150 mmHg or diastolic pressure ≥100 mmHg, despite treated with the optimal medicine), diabetes, etc.];

6. Patients who have symptoms of metastatic brain/meningeal tumors within 4 weeks of participation;

7. Ongoing adverse events>grade 1 at the time of participation (except hair loss and pigmentation);

8. Patients who have undergone major surgery or have not recovered from Invasive operation within 4 weeks prior to initiation of study treatment;

9. Coagulation disorders (INR >1.5, prothrombin time (PT) > ULN+4s or APTT >1.5ULN): with bleeding diathesis (such as active peptic ulcer) or receiving thrombolytic or anti-coagulant treatment;

10. Known pulmonary infection/ pneumonitis / interstitial pneumonia who are not suitable for the research;

11. Known active Hepatitis B or Hepatitis C virus infection;

    • if HBsAg result is positive, additional HBV DNA testing is required (the result is higher than the ULN of the research center);
    • if HCV antibody result is positive, additional HCV RNA testing is required (the result is higher than the ULN of the research center);

12. Known history of human immunodeficiency virus (HIV), or other acquired/congenital immune deficiency diseases or organ transplantation;

13. Other anti-tumor therapies are required (including radiotherapy, chemotherapy, immunotherapy, targeted treatment, traditional Chinese medicine, etc.);

14. Patients with known history of neurological or psychiatric disorders, including epilepsy or dementia;

15. Not suitable for the treatment assessed by the researchers;

16. Cardiac ejection fraction less than 50%;

17. Patients who have suffered from or are complicated with any other malignant tumor within 5 years (except radically resected skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, local prostate cancer, in situ cervical cancer or other carcinoma in situ).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
HA121-28 tables	HA121-28 tablets	Participants will receive oral HA121-28 at a starting dose of 25 mg once daily at the 1st day in 0 cycle and for 21 days on a 28-day treatment cycle

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (MTD) of HA121-28 tablets in Advanced and/or Metastatic Cancer Refractory to Standard Treatment	At the end of Cycle 1 (each cycle is 28 days)	MTD defined by dose limiting toxicities (DLTs) that occur in the first cycle. DLT defined as any clinically grade 3 or 4 non-hematologic toxicity as defined in the NCI CTC v4.0

Secondary Outcome Measures

Name	Time	Method
Antitumor Efficacy of HA121-28 tablets: RECIST criteria version 1.1.	up to 24 weeks	Efficacy evaluation done using RECIST criteria version 1.1.

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China