Combining Talimogene Laherparepvec With BRAF and MEK Inhibitors in BRAF Mutated Advanced Melanoma

• Status: Active, not recruiting
• Trial end date: 2021-06-30
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of the study is to determine safety and tolerability of the combination of talimogene laherparepvec in combination with dabrafenib and trametinib in BRAF mutated advanced melanoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: West Cancer Center
• Collaborators: Amgen; University of Tennessee Health Science Center
• Treatments: Dabrafenib; Talimogene laherparepvec; Trametinib

Criteria

Inclusion Criteria:

1. Age ≥ 18

2. Primary or recurrent Stage IIIB to IVM1c melanoma for whom surgery is not recommended

3. Activating BRAF mutation (limited to V600E or V600K mutations if being treated first-line, but can include any well-defined BRAF mutation after failure of prior immunotherapy)

4. Measurable disease defined as follows: At least one melanoma lesion that can be accurately and serially measured in one dimension and for which the longest diameter is ≥10 mm as measured by calipers, CT scan, or MRI.

a. If all lesions are lymph nodes, at least one node must be able to be accurately and serially measured in two dimensions, and the short-axis must be ≥15mm.

5. Injectable disease (defined as at least 1cm of disease in areas suitable for injection including cutaneous, subcutaneous, or nodal lesions)

Exclusion Criteria:

1. Prior therapy with talimogene laherparepvec

2. Prior therapy with the combination of dabrafenib and trametinib

3. Evidence of clinically significant immunosuppression such as the following:

1. Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease

2. Concurrent opportunistic infection

3. Receiving chronic systemic immunosuppressive therapy (> 2 weeks), including oral steroid doses > 10mg/day of prednisone or equivalent except for management of adverse events and CNS metastases during the course of the study. Subjects requiring intermittent use of bronchodilators or local steroid injections are not excluded.

4. Active herpes infection, herpes requiring chronic anti-herpetic therapy, or complications of prior herpetic infection (such as keratitis or encephalitis)

5. Chronic use of immunosuppressants or steroids (defined as prednisone 10mg/day or equivalent)

6. Clinically active cerebral metastases

7. History or evidence of melanoma associated with immunodeficiency states

8. History of other malignancy within prior 24 months with the exception of breast or bladder carcinoma in situ, and non-melanomatous skin cancer