A Phase I Study of HRS2300 or Combined With SHR-1316 or SHR-1701 or Trametinib or Almonertinib in Patients With Advanced Malignancies

A Multi-center, Open-Label，Dose Escalation and Dose Expansion Phase I Study of HRS2300 Monotherapy or Combined With SHR-1316 or SHR-1701 or Trametinib or Almonertinib in Patients With Advanced Malignancies

The study is being conducted to evaluate the safety and tolerability of HRS2300 and combined with SHR-1316 or SHR-1701 or trametinib or Almonertinib.To Determine the maximum tolerated dose (MTD) and recommended Dose (RP2D) for HRS2300 monotherapy and combination therapy.

Study Overview

• Status: Terminated
• Conditions: Advanced Malignancies
• Intervention / Treatment: Drug: HRS2300; Drug: HRS2300、 SHR-1316; Drug: HRS2300、SHR-1701; Drug: HRS2300、trametinib; Drug: HRS2300、Almonertinib

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18-75 years old，Male or female;
2. Patients with pathologically confirmed advanced solid tumors who did not respond to standard treatment, did not tolerate standard treatment, or were determined by the investigator to be unsuitable for standard treatment;
3. ECOG PS score of 0-1;
4. Life expectancy of ≥3 months;
5. Able and willing to provide a written informed consent.

Exclusion Criteria:

1. Receiving chemotherapy, targeted therapy, immunotherapy, radical radiotherapy or surgical treatment for less than 4 weeks before study therapy (excluding tyrosine kinase inhibitors or other small molecule targeted drugs < 2 weeks); Four weeks prior to the start of study treatment (patients who have entered the follow-up period measured by the time of last use of the experimental drug or device) were enrolled in another clinical study;
2. Drugs that affect the activity of metabolic enzyme CYP3A have been used in the past, and the eluting period from the end time to the first administration in this study is within 5 half-lives;
3. Patients with active TB within 1 year prior to the start of drug therapy or with a history of active TB infection more than 1 year prior to the start of drug therapy without proper treatment were studied;
4. Patients with other potential factors that may affect the study results or result in the premature discontinuation as determined by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group A	Drug: HRS2300; HRS2300 monotherapy
Experimental: Treatment group B	Drug: HRS2300、 SHR-1316; HRS2300 combined with SHR-1316
Experimental: Treatment group C	Drug: HRS2300、SHR-1701; HRS2300 combined with SHR-1701
Experimental: Treatment group D	Drug: HRS2300、trametinib; HRS2300 combined with trametinib
Experimental: Treatment group E	Drug: HRS2300、Almonertinib; HRS2300 combined with Almonertinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Dose limited toxicity（DLT）		Cycle 1( 4 weeks- monotherapy；3 weeks -combination）
Number of participants with adverse events		up to 3 years; at least once per treatment cycle
Determine RP2D of HRS2300 monotherapy and combination in patients with advanced malignancy	Enrolled sequentially from the initial dose of the trial, each subject received only one dose of the study drug and no other dose. The first subject of each dose should complete the first administration and be observed for 7 days before the other two subjects can be enrolled. After the DLT observation period of the last subject in each dose group has ended, the next dose increment can be entered. At the end of the dose escalation phase, the dose closest to the estimated toxicity probability of the target was selected as the MTD . At the end of the dose escalation, the SMC determined the RP2D based on the previous data.	through study completion，an average of 2 years

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2021
• Primary Completion (Actual): February 24, 2023
• Study Completion (Actual): May 23, 2023

Study Registration Dates

• First Submitted: August 31, 2021
• First Submitted That Met QC Criteria: September 9, 2021
• First Posted (Actual): September 17, 2021

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 17, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Trametinib
• Other Study ID Numbers: HRS2300-I-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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