A Phase I, Open label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti tumor Effects of Recombinant Oncolytic Virus M1 (M1 c6v1) for Treatment of Patients with Locally Advanced or Metastatic Solid Tumors

JRCT ID: jRCT2063230079

Registered date:15/12/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Solid Tumors
• Date of first enrollment: 15/12/2023
• Target sample size: 12
• Study type: Interventional
• Intervention(s): 3 cycles of 5 once daily IV injections for a total of 15 administrations

Outcome(s)

Primary Outcome

1. Evaluation of the safety and tolerability of M1-c6v1, determination of MTD/ multiple ascending dose (MAD)/ optimal biologically active dose (OBD) and the R2PD.
2. Assessment of the safety and tolerability of M1-c6v1 according to the frequency and nature of dose limiting toxicities and all AEs, defects and infections, serious adverse events (SAEs), AEs of special interest (AESI).

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Subjects must have diagnosis of locally advanced or metastatic solid tumors (including but not limited to liver cancer, cervical cancer, TNBC, colorectal cancer and prostate cancer) who are intolerable or refractory to the standard therapy.
2. Subject voluntarily agrees to participate in this study and signs an Institutional Review Board -approved informed consent prior to performing any of the Screening Visit procedures.
3. Males and females at least 18 years of age, inclusive, at the Screening Visit.
4. Have at least one measurable lesion.
5. An Eastern Cooperative Oncology Group (ECOG) score of 0-1, 1 week before the first administration of IMP.
6. An estimated survival time of >= 12 weeks.
7. Have sufficient organ function as shown below:
Blood system (subjects must not have received blood transfusion or hematopoietic stimulating factor treatment within 14 days)
Absolute neutrophil count (ANC)>= 1.5x(10 to the power of 9)/L
Platelets>= 100x(10 to the power of 9)/L (requirement for patients with primary liver cancer is >= 75x(10 to the power of 9)/L)
Haemoglobin (Hb)>= 90 g/L
Liver function
Total bilirubin (TBIL)<= 1.5 x upper limit of normal value (ULN) (subjects with Gilbert syndrome or liver metastasis/liver cancer <= 3.0 x ULN)
Alanine aminotransferase (ALT)<= 3.0 x ULN (subjects with liver metastasis or liver cancer <= 5.0 x ULN)
Aspartate aminotransferase (AST)<= 3.0 x ULN; (subjects with liver metastasis or liver cancer: <=5.0 x ULN)
Albumin>= 2.8 g/dL
Kidney function
Creatinine<= 1.5xULN;
Creatinine clearance rate (Ccr)>= 50 mL/min (calculated according to Cockcroft-Gault formula, Ccr is calculated only when creatinine > 1.5 x ULN)
Coagulation
Activated partial thromboplastin time (aPTT)<= 1.5 x ULN
International Normalized Ratio (INR) or Prothrombin Time (PT)<= 1.5 x ULN
Note: Prolongation of INR, PT and aPTT due to anticoagulant treatment is permitted, subject to the discretion of the investigator.
8. Women of childbearing potential (WOCBP) with a negative serum pregnancy test within 7 days prior to first administration of the IMP; or female of non-childbearing potential or postmenopausal, (surgically sterile [hysterectomy or oophorectomy] or postmenopausal (amenorrhea for more than 12 months with FSH in postmenopausal range confirmed by an FSH test).
9. WOCBP who agree to use medically acceptable forms of birth control (hormonal contraception, abstinence, diaphragm with spermicide, condom with spermicide or intrauterine device) from the Screening Visit until at least 90 days after the last dose of IMP. Breastfeeding women who agree not to breastfeed for at least 90 days after the last dose of study intervention.
10. Male subjects who agree to use highly effective birth control measures from the Screening Visit until at least 90 days after the last dose of IMP.
11. Study subjects must consent to stay in a private room at the trial site to be physically protected from mosquitoes for 2 h and then move to a general ward until discharge.

Exclude criteria

1. Subject has a history of primary or acquired immunodeficient states, leukemia, lymphoma, acquired immunodeficiency syndrome (AIDS) or other clinical manifestations of infection with human immunodeficiency viruses, and those on immunosuppressive therapy
2. Subject has received any anti-tumor treatment 4 weeks before using the IMP, including chemotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy, except for the following situations:
a) Received nitrosourea or mitomycin C within 6 weeks prior to first administration of IMP;
b) Received fluorouracils or small molecule targeted drugs 2 weeks prior to first administration of IMP or 5 half-lives of the drug (whichever is longer);
c) For subjects with non-central nervous system diseases treated with palliative radiotherapy, a 2-week washout period will be permitted but the subject must have recovered from any radiotherapy-related toxicity.
3. Subject has received systemic glucocorticoids (prednisone >10 mg/day or equivalent doses of similar drugs) or other immunosuppressive agents within 14 days prior to first administration of IMP, except for the following:
a) Topical, ocular, intra-articular, intranasal and inhaled corticosteroid therapy;
b) Short-term use of glucocorticoids for preventive treatment (such as prevention of contrast agent allergy).
4. Subject has received immunomodulatory drugs, including but not limited to thymosin, IL-2, IFN, etc. within 14 days prior to first administration of IMP.
5. Subject has received a live attenuated vaccine within 4 weeks prior to first administration of IMP, including but not limited to: measles, mumps, rubella, varicella/shingles, yellow fever, rabies, BCG and typhoid vaccine.
a) Seasonal influenza vaccine for injection will be permitted; the influenza vaccine for intranasal use will not be permitted.
6. Subject has received SARS-CoV-2 vaccine within 7 days prior to first administration of IMP.
7. Subject has previously received oncolytic virus or other gene drug therapy.
8. Subject has received an investigational drug within 4 weeks prior to first administration of IMP.
9. Subject has enrolled in another clinical study at the same time, except for the observational (non-interventional) clinical research or the follow-up phase of interventional research (whether it will affect efficacy and safety assessment of this research will be subject to the investigator's assessment).
10. Subject has undergone drug, major surgery under general anesthesia within 4 weeks prior to first administration of IMP; local anesthesia/epidural anesthesia within 2 weeks prior to first administration of IMP, or the subject has not recovered of either surgery; skin biopsies under local anesthesia completed in less than 1 hour will be exempt.
11. Subjects who have not yet recovered from the adverse reactions (NCI-CTCAE v5.0 <= Grade 1) of previous anti-tumor (except for toxicities with no safety risk as judged by the investigator, e.g., hair loss or Grade 2 neurotoxicity caused by chemotherapy).
12. Subjects who have brain tumors including primary gliomas and brain metastases.
13. Subjects who have a history of leptomeningeal disease.
14. Subjects who have a history of serious cardiovascular disease, including but not limited to:
a) Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia II-III degree or atrioventricular block that requires clinical intervention, QTcF interval >=480 ms;
b) Acute coronary syndrome, acute myocardial infarction, congestive heart failure, stroke or other cardiovascular events of grade 3 or above occur within 6 months before the first use of the IMP;
c) New York Heart Association (NYHA) cardiac function classification >= Grade II
d) The subject is judged by the investigator to have uncontrolled hypertension.
15. The subject has clinically uncontrollable third space effusion and is judged by the investigator to be unsuitable for inclusion.
16. Subjects who have a known history of tuberculosis infection.
17. Subject has active infection (any infection requiring systemic treatment), anti-human immunodeficiency virus antibody (anti-HIV antibody) positive, or active syphilis, or active hepatitis B (HBV) or hepatitis C (HCV) infection.
18. Subjects positive for both hepatitis C virus (HCV) antibody and HCV RNA. If the HCV antibody test is positive, but the HCV RNA test is negative, the subject may enroll in the study).
19. Subjects positive for hepatitis B surface antigen (HBsAg) or total hepatitis B core antibody (HBcAb) and with HBV DNA >=104 cps/mL, or >=2000 IU/mL.
20. Subjects are known to have an allergic reaction to any of the components in the M1-c6v1 formula (mannitol, human albumin, trehalose).
21. The investigator believes that the subject is not suitable for participating in this clinical study for other reasons.
22. Subjects known to have suffered from other malignant tumors not treated in the past 5 years, except those who have been cured.
23. Subjects known to have suffered from a known mental disorder or drug abuse disorder that may affect study compliance.
24. Participant who has been diagnosed with clinical COVID-19 within 14 days prior to screening.
25. Recent (within previous 14 days) exposure to someone who has COVID-19 symptoms or positive test result.

Related Information

• Primary Sponsor: Sawai Yoshihito
• Secondary ID(s): NCT06046742