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

NCT03088176 | Unknown Phase 1 FDA Drug

• 1 other identifier: WCC20149189
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Melanoma; BRAF Gene Mutation

Keywords

Melanoma; BRAF inhibitor; Intratumoral injection; Talimogene laherparepvec; MEK inhibitor; dabrafenib; trametinib

Outcome Measures

Primary Outcomes (1)

• Rate of Dose Limiting Toxicities (DLT)

  Number of DLT seen in the subject population

  2 years

Secondary Outcomes (5)

• Progression Free Survival

  4 years

• Objective Response Rate

  4 years

• Change in tumor burden

  4 years

• Time to Response

  4 years

• Duration of Response

  4 years

Other Outcomes (2)

• Lesion-level objective response

  4 years

• Biomarker analysis

  4 years

Study Arms (1)

Combination

EXPERIMENTAL

Talimogene laherperepvec intratumoral injection up to 4ml of 10\^6 PFU/mL on Day 1, followed by up to 4mL of 10\^8 PFU/mL 3 weeks later, followed by every 2 weeks thereafter for up to two years. Dabrafenib 150mg orally twice daily for up to two years Trametinib 2mg orally once daily for up to two years

Drug: Talimogene Laherparepvec 1 Million Pfu/Ml Inj,Susp,1Ml,Vil; Drug: Talimogene Laherparep 100 Mil Pfu/Ml 1Ml; Drug: Dabrafenib; Drug: Trametinib

Interventions

Talimogene Laherparepvec 1 Million Pfu/Ml Inj,Susp,1Ml,Vil DRUG

Up to 4mL administered on C1D1 intratumorally

Also known as: Imlygic

Combination

Talimogene Laherparep 100 Mil Pfu/Ml 1Ml DRUG

Up to 4 ML administered on Week 4 Day 1 and every 2 weeks thereafter

Also known as: Imlygic

Combination

Dabrafenib DRUG

150mg PO qday

Also known as: Tafinlar

Combination

Trametinib DRUG

2mg PO qday

Also known as: Mekinist

Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18
• Primary or recurrent Stage IIIB to IVM1c melanoma for whom surgery is not recommended
• 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)
• 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.
• Injectable disease (defined as at least 1cm of disease in areas suitable for injection including cutaneous, subcutaneous, or nodal lesions)

You may not qualify if:

• Prior therapy with talimogene laherparepvec
• Prior therapy with the combination of dabrafenib and trametinib
• Evidence of clinically significant immunosuppression such as the following:
• Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease
• Concurrent opportunistic infection
• 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.
• Active herpes infection, herpes requiring chronic anti-herpetic therapy, or complications of prior herpetic infection (such as keratitis or encephalitis)
• Chronic use of immunosuppressants or steroids (defined as prednisone 10mg/day or equivalent)
• Clinically active cerebral metastases
• History or evidence of melanoma associated with immunodeficiency states
• History of other malignancy within prior 24 months with the exception of breast or bladder carcinoma in situ, and non-melanomatous skin cancer

Sponsors & Collaborators

• West Cancer Center: lead
• University of Tennessee: collaborator
• Amgen: collaborator

Study Sites (1)

West Cancer Center

Germantown, Tennessee, 38138, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

talimogene laherparepvec; dabrafenib; trametinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: No masking
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 1b single arm single dose level

Study Record Dates

• First Submitted: March 7, 2017
• First Posted: March 23, 2017
• Study Start: June 25, 2017
• Primary Completion: November 30, 2020
• Study Completion: June 30, 2021
• Last Updated: October 12, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)