Overview
This is a Phase 1 open-label, non-randomized, multi-center clinical trial of intratumoral IVX037 in people with micro satellite-stable (MSS) colorectal or gastroesophageal cancer metastatic to liver, or advanced ovarian cancer.
Description
Participants will be enrolled by cohort, with a Safety Review Committee (SRC) reviewing any dose-limiting toxicities (DLT's) that develop within 21 days of the last dose of IVX037. If no DLT's are observed, the CRC may approve enrollment in the next study cohort.
Participants enrolled in the first two cohorts (one and two doses, respectively) who show stable disease or better at the Day 50 radiological assessment, may receive additional doses of IVX037, up to the maximum of 3 doses.
Following the dose escalation phase, up to 5 additional participants from each of the three tumour types, will be enrolled and receive IVX037 at the maximum tolerated dose. A total of fifteen (15) participants (5 from each of the 3 tumour types) at the maximum tolerated dose will provide paired tumour biopsies, one taken on Day 1 prior to IVX037 intratumoral injection and a second one taken two weeks later on Day 15. If the MTD occurs in Cohort 3, a third biopsy is requested on Day 29 (if possible) prior to IVX037 intratumoral injection. These biopsies will be used to assess for any changes in the tumour microenvironment.
Eligibility
1.1. Inclusion Criteria
- Histologically confirmed advanced colorectal, gastric/gastroesophageal adenocarcinoma, or ovarian cancer that has progressed or is not suitable for standard of care systemic therapies. Participants with colorectal cancer must have either a primary tumour or a biopsy of a metastatic tumour which has been shown to lack microsatellite instability (by PCR) or to have normal expression of mismatch repair enzymes (by immunohistochemistry). That is, a mismatch repair proficient mCRC tumour.
- At least one injectable tumour that meets RECIST1.1 criteria to be designated as a
target lesion, and is:
- a liver lesion ≥ 2 cm and ≤ 8 cm on baseline CT scan or MRI and suitable for injection under CT or ultrasound guidance, and has an estimated tumour volume < 1/3 of liver volume based on CT or MRI imaging, and no single metastatic lesion > 8 cm, or
- At least two tumours consisting of a measurable lymph node, i.e., with a short axis diameter (SAD) of ≥ 15 mm and/or other solid tumour with a longitudinal diameter ≥ 10 mm.
- Phase 1a at MTD dose: Fifteen (15) participants (5 of each tumour type) must provide a
biopsy (core needle, minimum 18 gauge) on Day 1 and Day 15.
- ECOG 0 or 1.
- Has adequate organ function defined in the protocol.
- Male or female 18 to 85 years of age.
- Must abstain from activities or use proper birth control methods for the duration of the study as defined in the protocol.
- Written, informed consent prior to the initiation of any study procedures.
- Female participants of child-bearing potential must have a negative urine pregnancy test within 72 hours prior to receiving the first dose of study medication.
- Life expectancy > 6 months.
1.2. Exclusion Criteria Medical Conditions
- Candidate for hepatic surgery or locoregional therapy for liver lesions with curative intent or requires other systemic anti-cancer therapy.
- Clinically significant ascites (Grade ≥2).
- Other concurrent uncontrolled illness, including mental illness or substance abuse, which may interfere with the ability of the subject to cooperate and participate in the trial; other examples of such conditions would include unstable or uncontrolled hypertension, unstable angina, myocardial infarction (MI) or cerebrovascular accident (CVA) within 6 months of study entry.
- Requires continuous systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 4 weeks prior to the first dose of study treatment should be an EC.
- Has not fully recovered from any effects of major surgery without significant detectable infection.
- Bleeding diathesis due to underlying medical conditions or the use of anticoagulation medications that is unable to be reversed by medical treatment.
- Tumors that lie close to an airway, major blood vessel or spinal cord, which, in the
opinion of the Investigator, could cause occlusion, compression, or erosion of the
vital structures.
Prior/Concomitant Therapy
- Participants who have been previously treated with an immune checkpoint inhibitor must have completed their last dose at least 21 days prior to Day 1, as long as there is demonstrated progressive disease during, or following the immune checkpoint inhibitor therapy.
- Participants who require prohibited treatments (i.e., non-protocol-specified
anticancer pharmacotherapy, surgery, or radiotherapy for treatment of malignancy).
Prior/Concurrent Clinical Study Experience
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- Participants who have received a live or inactivated vaccine within 4 weeks of the
first day of planned IVX037 treatment.
Diagnostic Assessments
- Participant with active (i.e., symptomatic or growing) CNS metastases. .
- Participant has a known history of HIV
- Active infection requiring systemic therapy.
- Known additional malignancy that is progressing or requires active treatment.
- A history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
Other Exclusions
- Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the Screening visit through 120 days after the last dose of trial treatment.