Testing KM1 for treating recurrent ovarian cancer

A Single-Arm, Open-Label Clinical Study to Evaluate the Safety, Tolerance and Preliminary Efficacy of KM1 Oncolytic Vaccinia Virus Injection Combined With Chemotherapy in Subjects With Recurrent or Refractory Ovarian Cancer

This study is testing a new treatment called KM1, which is a modified virus, to see if it can help people with recurrent ovarian cancer feel better when combined with chemotherapy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Tongji Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT05684731 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of KM1, a genetically modified oncolytic virus, in patients with recurrent or refractory ovarian cancer. Participants will receive intraperitoneal infusions of KM1, followed by chemotherapy, in two phases: Phase Ia with three doses and Phase Ib with six doses. The study aims to determine the recommended Phase 2 dose (RP2D) of KM1 and monitor participants for six months after the last chemotherapy dose to assess treatment outcomes.

Who should consider this trial

Good fit: Ideal candidates are patients with histologically confirmed recurrent or refractory epithelial ovarian cancer who have failed at least one platinum-based chemotherapy regimen.

Not a fit: Patients with mucinous ovarian cancer or those with unresolved toxicities from prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat ovarian cancer.

How similar studies have performed: Previous studies using oncolytic virus therapies have shown promising results in treating various solid tumors, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Histologically or cytopathology confirmed epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer, except mucinous cancer.
* Relapsed/refractory subjects who failed to receive systemic treatment (at least one standard platinum containing regimen); Note: If the disease relapses, there should be evidence showing imaging or clinical progress (such as cytological report of new ascites or pleural effusion). Only the increase of CA125 cannot be used as the standard of disease recurrence.
* Performance status ECOG of 0 or 1.
* Life expectancy of at least 3 months.
* Toxicities of prior therapies have not been resolved to Grade 1 or baseline (except for alopecia, pigmentation or other toxicity considered as no safety risk to the subject in the study).
* At least 1 measurable target lesion by RECIST 1.1.
* Adequate renal, hepatic, bone marrow function, adequate coagulation tests, adequate immune function by lymphocyte count.
* Pregnancy test results within 14 days before the treatment were negative. Subjects of childbearing age must agree to use at least one medically approved contraceptive measure (such as surgical sterilization, oral contraceptives, intrauterine devices, sexual desire control, etc.) during the study treatment and at least 6 months after the last trial drug treatment;
* Subjects voluntarily participated in the study, signed the informed consent form, had good compliance and cooperated with the follow-up.

Exclusion Criteria:

* • Central nervous system (CNS) metastasis or cancerous meningitis (Note: Subjects with treated CNS metastases may participate in this trial if the subject is neurologically stable ≥3 months).

  * Prior malignancy of other histology active within previous 3 years except for locally curable cancers apparently cured such as basal/squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of cervix or breast.
  * Received any of the following treatments within a specific time frame prior to enrollment:

    1. Have received surgery of Grade II or above within 4 weeks (Whether or not related to tumor), except minimally invasive surgery under gastrointestinal endoscopy;
    2. Have received radiotherapy within 2 weeks (the investigator can judge the appropriate time of enrollment according to the patient's toxicity recovery after radiotherapy);
    3. Within 4 weeks or participating in other therapeutic/interventional clinical studies;
    4. Have received local anti-tumor treatment within 4 weeks;
  * Allergic to the test drug or its active ingredients and excipients.
  * Has had severe allergic reaction after receiving smallpox vaccine in the past.
  * Has a history of severe skin diseases requiring systemic treatment within 2 years, such as eczema, atopic dermatitis, burns, seborrheic dermatitis, psoriasis, severe acne, etc.
  * Has had an allogenic tissue/solid organ transplant.
  * Active infection or fever of unknown cause (\>38.5 ℃).
  * Active pulmonary tuberculosis (TB) who are receiving anti tuberculosis treatment or who have received anti tuberculosis treatment within 1 year before screening;
  * Positive anti-HIV (+) or anti-HCV (+) or syphilis specific antibody (TPHA) or active hepatitis B.
  * Has a history of serious cardiovascular or cerebrovascular diseases, including but not limited to:

    1. New York Heart Association (NYHA) congestive heart failure of grade III or above;
    2. Serious arrhythmia requiring drug treatment;
    3. Acute myocardial infarction, severe or unstable angina, coronary or peripheral artery bypass grafting, and stenting occurred within 6 months;
    4. Left ventricular ejection fraction (EF)\<60%;
    5. QTcF interval ≥ 460 ms, or there are risk factors of torsade de pointes ventricular tachycardia, such as hypokalemia, family history of long QT syndrome or family history of arrhythmia (such as preexcitation syndrome);
    6. Presence of uncontrolled hypertension (systolic blood pressure \>160 mmHg or diastolic BP\>100 mmHg).
  * Active autoimmune diseases such as inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autohemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis), but the following conditions are allowed to enter the screening: type I diabetes, hypothyroidism that can be controlled only through alternative treatment, skin diseases that do not need systemic treatment (such as vitiligo, psoriasis or alopecia).
  * Symptomatic malignant ascites or pleural effusions defined as rapidly progressive ascites with abdominal distension and gastrointestinal dysfunction, pleural effusions with respiratory difficulties requiring frequent paracentesis \> once every 14 days.
  * Contraindications for intraperitoneal (IP) catheter placement: Bowel obstruction with distended abdomen, rigid abdomen with bulky anterior wall carcinomatosis, abdominal wall hernia mesh that precludes laparoscopic entry to abdomen.
  * Active gastrointestinal bleeding.
  * Accompanied by unstable mental illness, alcohol abuse, drug abuse or drug abuse.
  * Other conditions that investigator considers unsuitable for this study.

Where this trial is running

Wuhan, Hubei

• Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)

Study contacts

• Principal investigator: Qinglei Gao, MD. PhD — Tongji Hospital
• Study coordinator: Qinglei Gao, MD. PhD

Conditions Ovarian Cancer; KM1; oncolytic virus; immunotherapy