This is a Phase 1 Study of MH048 in Patients With Selected Relapsed/Refractory B-cell Malignancies

A Phase 1, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Antitumor Activity of MH048 in Subjects With Selected Relapsed/Refractory B-cell Malignancies

This is a Phase 1 study of MH048 in patients with selected Relapsed/Refractory B-cell Malignancies.

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory B-cell Malignancies
• Intervention / Treatment: Drug: MH048

Detailed Description

This is an open-label, multi-center Phase 1 study of MH048 in patients with selected Relapsed/Refractory B-cell Malignancies.

This study includes 2 parts: Part A is the dose escalation part of the study, and Part B is the dose expansion part of the study. In Part A, patients were enrolled using accelerated titration design for the first three single patient cohorts and 3+3 dose escalation design for the rest cohorts. The starting dose of MH048 in soft gel capsule form was 5 mg/day QD. Cycle length will be 28 days. In Part B, the dose and lymphoma subtypes for expansion phase will depend on the results from Part A.

• Study Type: Interventional
• Enrollment (Anticipated): 57
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jie Jin, MD; Phone Number: +86 057187236114; Email: jiej0503@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • the First Affiliated Hospita，Medicine School of Zhejiang University
      • Contact: Jie Jin, M.D.; Phone Number: +86-0571-87236114; Email: jiej0503@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female subjects ≥18 years of age;
2. Willing and able to understand and sign an informed consent form and to comply with all aspects of the protocol;
3. Life expectancy of ≥12 weeks;
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2;

5. Histologically confirmed B-cell Malignancies who have relapsed or are refractory to standard of care therapies, and have received ≥1 prior lines of therapy:

   Part A: Subjects with B-cell Malignancies (regardless of subtype); Part B: Subjects With Selected Relapsed/Refractory B-cell Malignancies based on data from Part A;

6. There must be radiographically measurable disease for effects assess at dose expansion cohort;

7. Adequate organ function, as specified below:

   Hematologic: Platelet count >65 × 10^9/L (may be posttransfusion, must one week before the first dose of starting study treatment); Hemoglobin (Hgb) ≥ 80 g/L; international normalized ratio (INR) or plasma prothrombin time (PT) ≤1.5 × ULN; absolute neutrophil count >1.0 × 10^9/L (growth factor use is allowed to bring pre-treatment neutrophils to >1.0 × 10^9 cells/L if bone marrow infiltration is involved, provided this is not within 7 days of starting study treatment); Hepatic: Total bilirubin <1.5 × upper limit normal (ULN), Total bilirubin <3 × ULN for Gilbert Syndrome; Aspartate aminotransferase (AST) and Alanine transaminase (ALT) ≤2.5 × ULN; Renal: Creatinine clearance ≥60 mL/min (as estimated by the Cockcroft-Gault equation );

8. Willing to have bone marrow biopsy/aspirate for baseline disease assessment and assessment of response to treatment;
9. Willingness of men and women of reproductive potential to observe conventional and highly effective birth control from the beginning of the study screening until 6 months after receiving the last treatment of investigational product. A fertile woman must be confirmed by a positive serum beta-human chorionic gonadotropin [β-hCG] test before 7 days of starting study treatment.

Exclusion Criteria:

1. History of other active malignancies within 1 years of study entry, with the exception of adequately treated in-situ carcinoma of cervix, localized basal cell or squamous cell carcinoma of skin, previous malignancy that was not recurred in 5 years;
2. History of allogeneic or autologous stem cell transplant or chimeric antigen receptor-modified T-cell (CAR-T) therapy within the past 100 days before starting study treatment, or diagnosis of graft vs host disease;
3. Clinically significant, uncontrolled cardiac or cardiovascular disease, or history of myocardial infarction, New York Heart Association (NYHA) Class III or IV, QTc prolongation (defined as a QTc > 450 ms) or other significant electrocardiogram (ECG) abnormalities including 2nd degree atrioventricular (AV) block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min) ,within 6 months prior to planned start of MH048 treatment;
4. Transformation (e.g., Richter's transformation, prolymphocytic leukemia, or blastoid lymphoma) prior to the planned start of MH048 treatment;
5. Subjects with known or suspected history of allergy to MH048 capsules or excipients;
6. Any unresolved toxicities from prior therapy of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v5.0) Grade 2 or higher at the time of starting MH048 treatment, with the exception of toxicities not considered a safety risk (eg, alopecia, neuropathy, or asymptomatic laboratory abnormalities);
7. Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection;
8. Active uncontrolled autoimmune disease;
9. Clinically significant active malabsorption syndrome;
10. Subjects with human immunodeficiency virus (HIV) , Active hepatitis B virus (HBsAg positive, or HBsAg negative/HBcAb positive ，and HBV DNA>10^3) or Active HCV infection (HCVAb positive ,and HCV RNA positive);
11. Major surgery within 4 weeks prior to planned start of MH048 treatment (expect for biopsy, laser eye surgery)；
12. Women of childbearing potential who are pregnant or lactating;
13. Subjects requiring therapeutic anticoagulation;
14. Radiotherapy with a limited field of radiation for palliation within 7 days of the first dose of MH048 treatment;
15. Received a CYP3A4, CYP2A8 strong inhibitor or inducer within 5 half-lives of planned investigational product administration；
16. Medical history of massive bleeding (hemophilia or other disease need the treatment of blood transfusion）;
17. Severe neurological/mental illness, and in the opinion of the Investigator, is unable to adhere to the requirements of the study;
18. Receipt of any investigational agent or clinical study within 28 days;
19. Unstable brain metastasis patient.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: Dose Escalation and Determination of RP2D; Part A: Dose Escalation and determination of RP2D, multiple dose levels of MH048 to be evaluated	Drug: MH048; Soft gel capsules 5 mg and 25 mg，oral MH048 should be administered after an overnight fast.; Other Names: MH048 Soft Gel Capsules
Experimental: Part B: Dose Expansion in Selected Relapsed/Refractory B-cell Malignancies; Part B: Selected relapsed/refractory B-NHL subjects with at least 1 prior systemic OR standard-of-care therapy.	Drug: MH048; Soft gel capsules 5 mg and 25 mg，oral MH048 should be administered after an overnight fast.; Other Names: MH048 Soft Gel Capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the incidence and severity of Treatment-Emergent Adverse Events [Safety and Tolerability]	Assess incidence and severity of treatment-emergent adverse events as determined by CTCAE v5.0	Up to approximately 24 Months
To determine the MTD of MH048	If 2 or more treated subjects at a dose level experience a DLT before Day 28, dose escalation will stop and the prior dose level will be considered the MTD for that schedule.	At the end of Cycle 1( 28 day) of each dose escalation cohort.
To establish the RP2D.	The determination of RP2D for phase 2 according to the result of dose expansion cohorts.	Up to approximately 24 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of Pharmacokinetics (Cmax)	Maximum drug concentration (Cmax)	At the end of Cycle 1 (each cycle is 28 days)
Characterization of Pharmacokinetics (AUC)	Area Under the Curve (AUC)	At the end of Cycle 1 (each cycle is 28 days)
Characterization of Pharmacokinetics (CL)	Clearance (CL)	At the end of Cycle 1 (each cycle is 28 days)
Characterization of Pharmacokinetics (t1/2)	Elimination half-life (t1/2)	At the end of Cycle 1 (each cycle is 28 days)
Preliminary evidence of anti-tumor activity, in terms of Objective Response Rate (ORR)	The number (%) of subjects with best overall response (BoR) of CR or PR.	From date of enrollment until the date of best overall response (BoR) of CR or PR, assessed up to approximately 24 months.
Preliminary evidence of anti-tumor activity, in terms of Duration of Response (DOR)	The duration from the first documentation of CR or PR to the first documented PD or death due to any cause, whichever occurs first.	From the first documented of CR or PR to the first documented PD or death due to any cause, whichever came first, , assessed up to approximately 24 months.

Collaborators and Investigators

• Sponsor: Minghui Pharmaceutical (Shanghai) LTD
• Investigators: Principal Investigator: Jie Jin, MD, 79 Qingchun Road, Shangcheng District, Hangzhou, Zhejiang, China

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2021
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: December 14, 2020
• First Submitted That Met QC Criteria: December 29, 2020
• First Posted (Actual): December 30, 2020

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: MH048-CP001CN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No