Clinical trial NCT05707325: Safety, Tolerability and Preliminary Efficacy of Engineered Red Blood Cell in Patients With Advanced Malignancies
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Cancer
Solid Tumor
Hematologic Malignancy
Keywords: solid tumors
hematologic malignancies
Lead sponsor: Westlake Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-01-31
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 21 days
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Overall Response Rate (ORR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: per 6 weeks
measure: Anti-drug antibody (ADA)
timeFrame: 1 year
measure: Maximum Concentration (Cmax) of engineered red blood cells in all Participants
timeFrame: Cycle 1: Pre-dose, post-dose at 0.5, 6 and 12 hours and Days 2, 3, 8 and 15
measure: Time to Maximum Concentration (Tmax) f engineered red blood cells in all Participants
timeFrame: Cycle 1: Pre-dose, post-dose at 0.5, 6 and 12 hours and Days 2, 3, 8 and 15
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Zhejiang Provincial People'S Hospital
state: Zhejiang
Study officials:
affiliation: ZHEJIANG PROVINCIAL PEOPLE'S HOSPITAL of China
name: xiangmin Tong, Phd
role: PRINCIPAL_INVESTIGATOR
References: