A Study of HS248 in Patients With Advanced Solid Tumors

Sponsor

Hanhui Pharmaceutical Co., Ltd (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05759234

Collaborator

(none)

Enrollment

Location

Arm

12.5

Anticipated Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a non-random, open multi-center study This study is a non-random, open multi-center phase I study, aimed at evaluation period research, aimed at In the evaluation phase study, it aims to evaluate the safety, tolerance PK characteristics and preliminary anti-tumor activity of HS248 in patients with advanced solid tumors. The study was divided into 2 phases, including dose escalation and dose expansion。

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor, Adult	Drug: HS248 pieces	Phase 1

Detailed Description

Main purpose:

Assess the safety and tolerability of HS248 in patients with advanced solid tumors, and determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of HS248.

Secondary purpose: Secondary purpose:

Assess the pharmacokinetic (PK) profile of HS248 in patients with advanced solid tumors; To evaluate the preliminary antitumor activity of HS248 in patients with advanced solid tumors. Preliminary antitumor activity in patients with advanced solid tumors.

Other purposes:

Population-based PK (PopPK) analysis method, exploratory description) analysis method, exploratory description) analysis method, exploratory description) analysis method, exploratory description of HS248 in patients with advanced solid tumors PK features in; Evaluate the relationship between exposure and efficacy and adverse events (AEs) of HS248 in patients with advanced solid tumors, as data permit; To explore the changes of HS248 in myeloid-derived suppressor cells (MDSC) and CD8+ T cells in patients with advanced solid tumors.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Intervention Model Description:

At this stage, it is planned that HS248 will adopt the traditional "3+3" method of increasing doses at four dose levels of 20 mg, 40 mg, 60 mg and 80 mg. All dosage components are divided into single administration stage and multiple administration stage. After 5 days of observation after single administration, it enters the stage of multiple administration. In the stage of multiple administration, HS248 is administered once a day (qd) for 28 days. a treatment cycle. 33 days after the first administration (the 5-day observation period in the single-administration phase and the first cycle in the multiple-administration phase) is the dose-limiting toxicity (DLT) observation period of this studyAt this stage, it is planned that HS248 will adopt the traditional "3+3" method of increasing doses at four dose levels of 20 mg, 40 mg, 60 mg and 80 mg. All dosage components are divided into single administration stage and multiple administration stage. After 5 days of observation after single administration, it enters the stage of multiple administration. In the stage of multiple administration, HS248 is administered once a day (qd) for 28 days. a treatment cycle. 33 days after the first administration (the 5-day observation period in the single-administration phase and the first cycle in the multiple-administration phase) is the dose-limiting toxicity (DLT) observation period of this study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of HS248 in the Treatment of Patients With Advanced Solid Tumors

Actual Study Start Date :

Nov 15, 2022

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HS248 pieces dose escalation period： At this stage, it is planned that HS248 will adopt the traditional "3+3" method of increasing doses at four dose levels of 20 mg, 40 mg, 60 mg and 80 mg. All dosage components are divided into single administration stage and multiple administration stage. After 5 days of observation after single administration, it enters the stage of multiple administration. In the stage of multiple administration, HS248 is administered once a day (qd) for 28 days. a treatment cycle. 33 days after the first administration (the 5-day observation period in the single-administration phase and the first cycle in the multiple-administration phase) is the dose-limiting toxicity (DLT) observation period of this study	Drug: HS248 pieces The overall safety and tolerability of PI3Kγ inhibitor monotherapy for solid tumors is good, and it has shown preliminary clinical benefits. The safety of PI3Kγ inhibitor combined with immune checkpoint inhibitor is good, and the efficacy of single drug is significantly improved. Based on the evaluation of the safety and efficacy results of HS248 preclinical and clinical studies of similar PI3Kγ inhibitors, the benefits of this product outweigh the risks for patients with advanced solid tumors who have progressed through standard treatment, have toxicity intolerance, or have no standard treatment regimen. Sufficient to support planned clinical studies.

Arm

Intervention/Treatment

Experimental: HS248 pieces

dose escalation period： At this stage, it is planned that HS248 will adopt the traditional "3+3" method of increasing doses at four dose levels of 20 mg, 40 mg, 60 mg and 80 mg. All dosage components are divided into single administration stage and multiple administration stage. After 5 days of observation after single administration, it enters the stage of multiple administration. In the stage of multiple administration, HS248 is administered once a day (qd) for 28 days. a treatment cycle. 33 days after the first administration (the 5-day observation period in the single-administration phase and the first cycle in the multiple-administration phase) is the dose-limiting toxicity (DLT) observation period of this study

Drug: HS248 pieces

The overall safety and tolerability of PI3Kγ inhibitor monotherapy for solid tumors is good, and it has shown preliminary clinical benefits. The safety of PI3Kγ inhibitor combined with immune checkpoint inhibitor is good, and the efficacy of single drug is significantly improved. Based on the evaluation of the safety and efficacy results of HS248 preclinical and clinical studies of similar PI3Kγ inhibitors, the benefits of this product outweigh the risks for patients with advanced solid tumors who have progressed through standard treatment, have toxicity intolerance, or have no standard treatment regimen. Sufficient to support planned clinical studies.

Outcome Measures

Primary Outcome Measures

Safety and tolerability [From first dose of HS248 through 28 days after the last HS248 treatment (up to 2 years); each cycle is 28 days]
To examine the incidence of clinical and laboratory adverse events after multiple doses of HS-248 in the dose escalation and dose expansion phases
MTD and/or RP2DP2D [The end of the study is defined as the last subject completing the last visit, study treatment for 2 years, loss to follow-up, death or withdrawal of informed consent, whichever occurs first]
MTD and/or RP2DP2D

Secondary Outcome Measures

Peak Plasma Concentration (Cmax) [From date of initial dose until up to 33 days for treatment]
Cmax of HS248
Area Under the Plasma Concentration versus Time Curve (AUC) [From date of initial dose until up to 33 days for treatment]
AUC of HS248
ORR [Up to 2 years]
Objective Response Rate
DOR [Up to 2 years]
Duration of Remission
PFS [Up to 2 years]
Progression-Free Survival
DCR [Up to 2 years]
Disease Control Rate
OS [Up to 2 years]
Overall Survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Voluntarily participate in this clinical trial, understand and follow the research procedures and voluntarily sign the ICF;
Male or female, age ≥18 when signing the ICF;
Expected survival period ≥ 12 weeks;
Patients with advanced solid tumors confirmed by histology/cytology, who have progressed through standard treatment, have toxicity intolerance, or have no standard treatment plan (patients with multiple solid tumors are included in the dose-escalation phase, and the population included in the dose-expansion phase will be based on dose escalation phase study data and the potential advantageous population of similar drugs);
Eastern Cooperative Oncology Group (ECOG) physical status score 0-1

Exclusion Criteria:

Symptomatic or untreated central nervous system metastasis or primary central nervous system malignancy;
Other known malignant tumors in the past 5 years, except cured localized tumors, including carcinoma in situ of the cervix, basal cell carcinoma of the skin, and carcinoma in situ of the prostate;
Previous history of autoimmune diseases, stem cell transplantation or organ transplantation;
Known drug-induced liver injury, chronic active hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, persistent extrahepatic obstruction caused by gallstones, cirrhosis or portal hypertension;
Peptic ulcer and/or gastrointestinal bleeding at present or in the past;
Gastrointestinal dysfunction that may limit the absorption of the test drug, including motility disorders, malabsorption syndrome or inflammatory bowel disease;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Cancer Hospital	Beijing	Beijing	China

Sponsors and Collaborators

Hanhui Pharmaceutical Co., Ltd

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Hanhui Pharmaceutical Co., Ltd

ClinicalTrials.gov Identifier:

NCT05759234

Other Study ID Numbers:

HS248-I-01

First Posted:

Mar 8, 2023

Last Update Posted:

Mar 8, 2023

Last Verified:

Feb 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Neoplasms

Study Results

No Results Posted as of Mar 8, 2023