Pilot study to examine the effects of combined XPO1/PD-1 inhibition in canine cutaneous T cell lymphoma

The purpose of this study is to evaluate the effectiveness of a new combination therapy for epitheliotropic cutaneous T cell lymphoma (CTLC) an aggressive skin cancer that occurs in dogs. While most dogs respond initially to treatment, resistance develops quickly and often dogs fail all therapies within 5 months. In the current study, a new oral drug (verdinexor, also known as Laverdia) that targets a key cancer protein called XPO1 will be combined with a new antibody (gilvetmab) that works to activate the immune system by targeting a protein called PD-1. Verdinexor and gilvetmab are both drugs that have been specifically developed to treat dog cancers and have shown activity when given alone. A recent study in people with T cell cancers showed that when these types of drugs are given together (selinexor, also an XPO1 inhibitor, plus tislelizumab, a human anti-PD-1 antibody), the combination is very active, with most affected patients achieving a complete response to treatment. Based on these encouraging results, we will test the combination of verdinexor and gilvetmab in dogs with CTCL.

Inclusion Criteria

• Must have histopathologic diagnosis of epitheliotropic CTCL with more than one measurable lesion, each of which must be at least 2 cm in size.
• Must be at least 1 year of age and weigh 8 kg or higher.
• Must have adequate organ function as indicated by standard laboratory tests.
• Must have an ECOG performance score of 0-1 and life expectancy of 28 days.

Exclusion Criteria

• Must have no underlying significant cardiac, renal or hepatic disease.
• Must not have received verdinexor or a prior immunotherapy regimen.
• Must not use complementary or alternative medicines while on study.
• Must not have any serious systemic disorder incompatible with the study (at the discretion of the principal investigators).

Client Benefits

The study covers all costs associated with the procedures involved except the routine blood work at each study visit (CBC and chemistry panel) after screening. The estimated cost per study visit is $100-$150. Side effects related to the drug treatment will be covered by the study. However, treatment of other conditions (bladder infection, ear infection, etc.) is not covered by the study.

Sample or Data Requirements

If your dog is deemed eligible for enrollment based on screening physical exam and bloodwork (diagnosis of cutaneous T cell lymphoma, eating/drinking normally and free of any other serious conditions such as heart/kidney/ liver disease), your dog will first undergo study blood collection and a punch biopsy of the tumor in the skin. Your dog will then receive verdinexor orally twice per week, and gilvetmab given by intravenous infusion every 2 weeks for a total of 4 treatments. Blood (approximately 1 tablespoon) will be collected at each visit to check cell counts and organ function, as well as for study purposes. At Week 8 of the study (2 weeks post gilvetmab #4) a second punch biopsy will be taken.

If your dog has responded to treatment (partial or complete response), then the verdinexor and gilvetmab will be continued for another 2 treatments, although the frequency of administration will be reduced to every 4 weeks. The final study visit will take place one month after the last gilvetmab dose at which point another skin biopsy will be taken. If your dog is still experiencing benefit from the treatment then the verdinexor can be continued for another 6 months. The gilvetmab will not be given beyond the last planned treatment.