Safety, Tolerability and Preliminary Efficacy of Engineered Red Blood Cell in Patients With Advanced Malignancies (Reboot-101)

A Multicenter, Single-arm, Open-label, Dose-escalation and Dose-expansion Clinical Study Evaluating the Safety, Tolerability and Preliminary Efficacy of Engineered Red Blood Cell in Patients With Advanced Malignancies

This is an investigator-initiated trial aimed at evaluating the safety and preliminary efficacy of a novel red blood cell-based therapy, where engineered red blood cells are conjugated with checkpoint inhibitors.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Solid Tumor; Hematologic Malignancy
• Intervention / Treatment: Drug: engineered red blood cell

Detailed Description

The present study has 2 parts，including dose escalation and dose expansion。The dose escalation part is carried out according to the "3+3" increasing principle. At least four dose groups are predefined based on the number of engineered red blood cells, specifically 1e11, 2e11, 3e11, 3.5e11,etc.

Dose expansion part will be decided according to dose escalation part.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: xiangmin Tong, Phd; Phone Number: +86-13750816623; Email: tongxiangmin@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310014
      • Recruiting
      • Zhejiang Provincial People's Hospital
      • Contact: Tong Xiangmin, Ph.D; Phone Number: 13750816623; Email: tongxiangmin@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1.Histologically- or cytologically-proven advanced malignancies;
• 2.Male or female, 18 years of age or older but no more than 75 at the time of signing informed consent;
• 3.Dose escalation stage: (1) patients with advanced solid tumors who have received at least 2 regimens, and PDx monotherapy or combination therapy is included in the last regimen ; or patients received 1st regimen or above who cannot tolerate standard therapy but PDx monotherapy or combination therapy should be included in the last regimen.(2)Patients with relapsed and refractory malignant lymphomas (including: classic Hodgkin lymphoma (cHL), primary mediastinal large B-cell lymphoma PMBCL , Extranodal NK/T-cell lymphoma ENKTCL, mycosis fungoides/Sezari syndrome MF/SS) , or patients have no standard therapy, or are unable to receive standard therapy, PDx monotherapy or combination therapy is used in the last regimen.(3)All patients did not receive systemic therapy after disease progression and the time of disease progression cannot exceed 3 months, radiotherapy was acceptable (definition of secondary resistance: achieved disease control (including CR/PR/ SD), but then disease progression after PDx therapy);
• 4.Dose expansion stage:(1)patients with advanced solid tumors who have received at least 1 regimen or these is no standard systematic therapy or patients can not recieve standard therapy, but PDx monotherapy or combination therapy should be included in the last regimen.(2)patients with relapsed and refractory malignant lymphomas who have no standard therapy or can not receive standard therapy, but PDx monotherapy or combination therapy should be included in the last regimen.(3)All patients did not receive systemic therapy after disease progression and the time of disease progression cannot exceed 3 months, radiotherapy was acceptable (definition of secondary resistance: achieved disease control (including CR/PR/ SD), but then disease progression after PDx therapy);
• 5.Solid tumor：at least one lesion that is measurable according to RECIST 1.1;lymphomas:at least one visble or evaluable lesion that is measurable according to Lugano2014;
• 6.Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
• 7.Take the shorter one as the washout period before experimental treatment (28 days after the last tumor treatment, or 5 half lives);
• 8.Resolution of all acute reversible toxic effects of prior therapy or surgical procedure to baseline or Grade ≤1 (except alopecia and peripheral neurotoxicity);
• 9.Adequate organ function;
• 10.Estimated life expectancy of ≥12 weeks;
• 11.Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF).

Exclusion Criteria:

• 1.Any active or recently diagnosed clear or suspected autoimmune disorder disease;
• 2. Other serious medical diseases, including but not limited to: uncontrolled diabetes, active peptic ulcer, liver cirrhosis, active bleeding, etc., and those with uncontrolled or serious cardiovascular disease, such as the NYHA II or higher heart failure, unstable angina, myocardial infarction and other cardiovascular disease within 6 months before first administration, and uncontrolled hypertension (systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 100 mmHg);
• 3.Has known active Hepatitis B or Hepatitis C or HIV;
• 4.Active brain metastases and/or cancerous meningitis;
• 5.Known history of any diseases affecting the quality and stability of erythropoiesis;
• 6.The spleen has been removed or, as judged by the investigator, a splenectomy may be planned during the trial;
• 7.Received at least one alive virus vaccination within 6 months before the first dose (except for the COVID-19 inactivated vaccine);
• 8.Known history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severely impaired lung function, etc.

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: Dose Escalation in Solid tumors and Hematologic malignancies; In Dose Escalation part， all patients will be enrolled in different doses according to the Study Protocol for evaluate the recommend dose	Drug: engineered red blood cell; engineered red blood cell
Experimental: Dose Expansion in Solid tumors and Hematologic malignancies; In Expansion part， all patients will be enrolled in recommended dose	Drug: engineered red blood cell; engineered red blood cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v.5.0) in Participants in escalating part.	DLTs were assessed according to NCI-CTCAE v.5.0 during the first cycle (21 days) and were defined as occurrence of any of the following toxicities if judged by the investigator to be possibly, probably or definitely related to study drug administration。	21 days
Number of Participants Who Experienced an Adverse Event (AE)	An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of the Sponsor's product was also an AE. The number of participants who experienced an AE was reported for all patients.	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)	ORR was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1(only for solid tumor) or Lugano2014( only for lymphomas)	per 6 weeks
Anti-drug antibody (ADA)	Describe the number and percentage of anti-drug antibodies (ADA) produced by subjects at each time point after treatment, and the time of producing ADA.	1 year
Maximum Concentration (Cmax) of engineered red blood cells in all Participants	Blood samples were collected at specified intervals for the determination of Cmax. Cmax was defined as the maximum concentration of engineered red blood cells reached. Cmax was based on noncompartmental analysis and reported for all participants	Cycle 1: Pre-dose, post-dose at 0.5, 6 and 12 hours and Days 2, 3, 8 and 15
Time to Maximum Concentration (Tmax) f engineered red blood cells in all Participants	Blood samples were collected at specified intervals for the determination of Tmax. Tmax was defined as time to the maximum concentration of engineered red blood cells reached. Tmax was based on noncompartmental analysis and reported for all participants	Cycle 1: Pre-dose, post-dose at 0.5, 6 and 12 hours and Days 2, 3, 8 and 15

Collaborators and Investigators

• Sponsor: Westlake Therapeutics
• Investigators: Principal Investigator: xiangmin Tong, Phd, ZHEJIANG PROVINCIAL PEOPLE'S HOSPITAL of China

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: January 21, 2023
• First Posted (Actual): January 31, 2023

Study Record Updates

• Last Update Posted (Actual): July 24, 2024
• Last Update Submitted That Met QC Criteria: July 22, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: solid tumors; hematologic malignancies
• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: Reboot-101

Drug and device information, study documents

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