-Have pathologically confirmed, advanced, unresectable, or metastatic solid tumors. Preferred indications include, but are not limited to, breast carcinoma, bladder carcinoma, cervical squamous carcinoma, colorectal carcinoma, esophageal carcinoma, head and neck squamous carcinoma, renal cell carcinoma, ovarian carcinoma, sarcoma, thymoma, and uterine carcinoma.
- Failed, intolerant to, or refused potentially curative treatment options, including but not limited to, standard of care molecularly targeted agents, immunotherapy (e.g., anti -pembrolizumab/PDL1 antibodies), and chemotherapy
- Measurable disease as per RECIST 1.1 criteria
- At least one tumor amenable to safe ITu injections and/or biopsies
- ECOG performance status 0 or 1
- Demonstrate adequate organ function
- Must be willing to comply with all protocol procedures and adhere to post-treatment care instructions
Additional Inclusion criteria exist
Key Exclusion Criteria:
- Prior systemic therapy washout (dependent upon the therapy)
- Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies or intra-tumoral injections.
- CNS metastases and/or carcinomatous meningitis that have not been completely resected or completely irradiated.
- Prior history of myocarditis
- Known HIV/AIDS, active HBV or HCV infection.
- Receiving high dose immunosuppressive medication or has a significant immunodeficiency (e.g. transplant recipient, etc).
- Additional Exclusion criteria exist
A Phase I/Ib Study of VET3-TGI Administered Alone and in Combination with Pembrolizumab in Patients with Advanced Solid Tumors
Details
VET3-TGI was changed in a laboratory to infect and kill cancer cells, leaving healthy cells alone. This is a Phase 1 dose escalation (and expansion) study with VET3-TGI administered by direct injection into tumor(s) or by intravenous infusion. The dose escalation has 4 groups: the first group (Group A) will determine the highest tolerated dose of VET3-TGI when injected into tumor(s); the second group (Group C) will determine the highest tolerated dose of VET3-TGI when infused into the vein. The third and fourth groups (Group B and D) will combine VET3-TGI with pembrolizumab. These groups will begin at the highest tolerated dose determined in Group B and Group D, respectively.
Once the highest tolerated dose is found for each of these groups, that dose may be expanded to up to 15 additional patients to better examine the efficacy of VET3-TGI.
Eligibility
You can join if...
Inclusion Criteria
Be equal or greater than 18 years of age (or legal age of majority in the jurisdiction) on day of signing informed consent
Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Have measurable disease based on RECIST 1.1, with one or more safely biopsiable tumor(s).
. Have pathologically confirmed, advanced, unresectable, or metastatic solid tumors. Preferred indications include, but are not limited to, breast carcinoma, bladder carcinoma, cervical squamous carcinoma, colorectal carcinoma, esophageal carcinoma, head and neck squamous carcinoma, renal cell carcinoma, ovarian carcinoma, sarcoma, thymoma, and uterine carcinoma.
Failed, intolerant to, or refused potentially curative treatment options, including but not limited to, standard of care molecularly targeted agents, immunotherapy (e.g., anti pembrolizumab/PDL1 antibodies), and chemotherapy
Failed, refused, or intolerant to at least 2 lines of palliative chemotherapy (as applicable for tumor indications with palliative therapy options, as determined by the Investigator
Demonstrate adequate organ function
To prevent the risk of environmental shedding, all patients must be willing to use barrier contraception (will be outlined in final protocol), during sexual activity, starting with Week 0/Day 1 for up to 6 weeks after each dose of VET3-TGI.
Meet the following criteria to prevent pregnancy
Patients must be willing to comply with study-mandated procedures including biopsies, imaging, and other procedures. Patients who withdraw consent for these procedures will be withdrawn from the trial
Exclusion Criteria
Has received systemic anti-cancer therapy
Has any of the following within 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, pulmonary embolism, uncontrolled hypertension, or uncontrolled congestive heart failure. New York Heart Association (NYHA) functional classification ≥3 are excluded (with or without cardiac clearance).
Has used excluded antiviral medication (e.g., interferon/peg-interferon, ribavirin) within 14 days of Week 0/Day 1 that cannot be suspended throughout the study for at least 14 days prior to and after each treatment with VET3-TGI.
Has had prior treatment with any vaccinia-based therapy.
Requires use of antiplatelet or anticoagulant therapy that cannot be safely suspended for study-specified injections, biopsies, and other procedures as per standard of care. Refer to Section 8.2 in the STEALTH-001 ITu Injection Procedure and Biopsy Guidance Manual
Has significant immunodeficiency due to underlying illness (e.g., known HIV/AIDS).
Has received systemic immunosuppressive medication including high-dose corticosteroids (e.g., systemic corticosteroids >10 mg prednisone or equivalent), within 14 days prior to Week 0/Day 1 or other immunosuppressive medications within 30 days of Week 0/Day 1. Topical steroids (used >12 inches from a superficial lesion to undergo VET3-TGI injection), ocular, intra-articular, intranasal, and inhalational corticosteroids with minimal systemic
absorption, and adrenal replacement steroid doses ≤10 mg daily prednisone equivalent, are permitted, in the absence of active autoimmune disease
Has had an allogenic tissue/solid organ transplant
Has received prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered (i.e., ≤Grade 1 or at Baseline) from all radiation-related toxicities and must not be taking corticosteroids (except as allowed above in Exclusion Criterion 7). A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease. No patients with radiation pneumonitis >Grade 1, asymptomatic (diagnostic observations only), may be enrolled.
Has a known additional malignancy that is progressing or has requi