Safety, Tolerability and Preliminary Efficacy of Engineered Red Blood Cell in Patients With Advanced Malignancies

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 ofsigning informed consent;

• 3.Dose escalation stage: (1) patients with advanced solid tumors who have receivedat least 2 regimens, and PDx monotherapy or combination therapy is included in thelast regimen ; or patients received 1st regimen or above who cannot toleratestandard therapy but PDx monotherapy or combination therapy should be included inthe last regimen.(2)Patients with relapsed and refractory malignant lymphomas (including: classic Hodgkin lymphoma (cHL), primary mediastinal large B-celllymphoma PMBCL , Extranodal NK/T-cell lymphoma ENKTCL, mycosis fungoides/Sezarisyndrome MF/SS) , or patients have no standard therapy, or are unable to receivestandard therapy, PDx monotherapy or combination therapy is used in the lastregimen.(3)All patients did not receive systemic therapy after disease progressionand the time of disease progression cannot exceed 3 months, radiotherapy wasacceptable (definition of secondary resistance: achieved disease control (includingCR/PR/ SD), but then disease progression after PDx therapy);

• 4.Dose expansion stage:(1)patients with advanced solid tumors who have received atleast 1 regimen or these is no standard systematic therapy or patients can notrecieve standard therapy, but PDx monotherapy or combination therapy should beincluded in the last regimen.(2)patients with relapsed and refractory malignantlymphomas who have no standard therapy or can not receive standard therapy, but PDxmonotherapy or combination therapy should be included in the last regimen.(3)Allpatients did not receive systemic therapy after disease progression and the time ofdisease progression cannot exceed 3 months, radiotherapy was acceptable (definitionof secondary resistance: achieved disease control (including CR/PR/ SD), but thendisease 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 accordingto 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 daysafter the last tumor treatment, or 5 half lives);

• 8.Resolution of all acute reversible toxic effects of prior therapy or surgicalprocedure 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 therequirements 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: uncontrolleddiabetes, active peptic ulcer, liver cirrhosis, active bleeding, etc., andthose with uncontrolled or serious cardiovascular disease, such as the NYHA IIor higher heart failure, unstable angina, myocardial infarction and othercardiovascular disease within 6 months before first administration, anduncontrolled hypertension (systolic blood pressure ≥ 180 mmHg and/or diastolicblood 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 oferythropoiesis;

• 6.The spleen has been removed or, as judged by the investigator, a splenectomy maybe planned during the trial;

• 7.Received at least one alive virus vaccination within 6 months before the firstdose (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.