A Phase 2 Study of HX301 in Patients with High-grade Giloma

Official title

A Phase IIa Clinical Study of HX301 Alone or in Combination with Temozolomide in Patients with High-Grade Glioma (Grade III and IV)

Overview

The study will include a dose-escalation and dose-expansion component to establish the recommended Phase 2 dose (RP2D) for HX301 in combination with Temozolomide and to evaluate the preliminary antitumor activity of HX301.HX301 is an investigational drug that has not yet been approved by the Food and Drug Administration (FDA) or any other regulatory authorities for commercial purposes.

Interventions

• Drug HX301+/Temozolomide
  Part I: It is planned to firstly explore a dose of 160 mg and enroll approximately 3-6 subjects to receive HX301 monotherapy until disease progression, intolerable toxicity, or other reasons for stopping treatment for up to 24 cycles of 28 days each. Safety evaluation was performed using the traditional "3 + 3" rule, and the DLT observation period was 28 days (C1D1 \~ C1D28). If 160 mg was not tolerated, it was reduced to 120 mg for exploration. Part II: Combination therapy phase: HX301 will be

Primary outcome measures

• Part I: Number of participants experiencing Adverse Events (AEs) [Time frame: All AEs up to 28(±7)days after the last dose of study treatment]
• Part I: Identify the recommended phase IIa dose (RP2D) of HX301 in patients with high-grade glioma; [Time frame: 24 Cycles of 28 days each.]
• Part II (HX301 monotherapy safety run-in period) : Number of participants experiencing Adverse Events (AEs) [Time frame: All AEs up to 28(±7)days after the last dose of study treatment]
• Part II (HX301 monotherapy safety run-in period) : Identify the recommended phase IIa dose (RP2D) of HX301 combination with TMZ in patients with high-grade glioma; [Time frame: 24 Cycles of 28 days each.]
• Part II (HX301 in combination with temozolomide) : Progression-free survival（PFS） per Investigator assessed using RANO criteria. [Time frame: 24 Cycles of 28 days each.]
• Part II (HX301 in combination with temozolomide) :Objective response rate（ORR） per Investigator assessed using RANO criteria. [Time frame: 24 Cycles of 28 days each.]

Secondary outcome measures (3)

• Part I : Objective response rate（ORR） per Investigator assessed using RANO criteria. [Time frame: 24 Cycles of 28 days each.]
• Part II (HX301 monotherapy safety run-in period) : Objective response rate（ORR） per Investigator assessed using RANO criteria. [Time frame: 24 Cycles of 28 days each.]
• Part II (HX301 in combination with temozolomide) :Overall survival（OS） per Investigator assessed using RANO criteria. [Time frame: 24 Cycles of 28 days each.]

Eligibility criteria

Inclusion criteria

• Signed informed consent form;
• Age ≥ 18 years;
• Expected survival ≥ 12 weeks;
• Part I:1) Histologically confirmed high-grade glioma (WHO classification grade III or IV); 2) At least one prior temozolomide treatment; 3) Patients with recurrent or progressive clinically assessed disease according to RANO criteria with evaluable lesions; Part II: Patients with histological or cytological diagnosis of glioblastoma according to World Health Organization (WHO) classification (2021) who received surgical treatment for the first time and standard concurrent chemoradiotherapy and who have not received any other prior treatment;
• Part II: Subjects must undergo partial or complete surgical resection, and available results of postoperative brain contrast-enhanced MRI were documented as follows: 1) complete resection without gadolinium enhancement ; or 2) complete resection (80% or more);
• Part II: Subjects must complete initial radiotherapy combined with TMZ (concurrent chemoradiotherapy) for glioblastoma according to the Stupp regimen (Stupp 2005) (total radiation dose 5 4-60 G y);
• Part I: If radiotherapy has been performed, the completion of radiotherapy shall last for 3 months, or there shall be tumor progression or histopathological confirmation of progression in the original radiation field within 3 months; Part II: there shall be no evidence of disease progression after chemoradiotherapy, except for pseudo progression;
• Dexamethasone was administered at ≤ 5 mg/day at study entry.Corticosteroids should be reduced as far as possible to the smallest dose necessary to control neurological symptoms before receiving study treatment;
• Karnofsky performance status (KPS) ≥ 70 within 1 4days prior to receiving study treatment ;
• Willing and able to comply with the protocol.

Exclusion criteria

• Part II: Patients with recurrent glioblastoma;
• Distant metastasis involving brainstem and meninges or extension of lesions to spinal cord;
• Human immunodeficiency virus (HIV) antibody positive, syphilis antibody (Anti-TP) positive, hepatitis C virus (HCV) antibody positive and HCV RNA positive, hepatitis B virus surface antigen (HBsAg) positive and HBV DNA positive (HBsAg positive requires further detection of HBV DNA, HBV DNA ≥ 200 IU/ml, or ≥ 10 3 copies/ml);
• Hypersensitivity to temozolomide and/or components of HX301;
• At risk for torsades de pointes (TdP): patients with a marked prolongation of the QT/QTc interval calculated using the Fredericia QT correction formula at baseline (eg, repeated demonstration of QTc interval > 470 ms), or a history of other TdP risk factors (eg, heart failure, hypokalemia, family history of long QT syndrome), or patients who are currently taking medications that prolong the QT/QTc interval;
• Grade ≥ 2 diarrhea at baseline;
• Participation in another study involving an investigational drug within 30 days prior to the first dose of study drug;

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Tiantan Hospital Capital Medical University — Beijing

Identifiers

NCT: NCT06703255 · HX301-II-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗