Combining Talimogene Laherparepvec With BRAF and MEK Inhibitors in BRAF Mutated Advanced Melanoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03088176|
Recruitment Status : Recruiting
First Posted : March 23, 2017
Last Update Posted : October 1, 2019
|Condition or disease||Intervention/treatment||Phase|
|Melanoma BRAF Gene Mutation||Drug: Talimogene Laherparepvec 1 Million Pfu/Ml Inj,Susp,1Ml,Vil Drug: Talimogene Laherparep 100 Mil Pfu/Ml 1Ml Drug: Dabrafenib Drug: Trametinib||Phase 1|
While targeted therapies can successfully block oncogenic signaling in BRAF mutant melanoma, activation of an immune response with agents such as talimogene laherparepvec can induce durable responses in a subset of patients. Combining BRAF inhibitors and immunotherapy may specifically target the BRAF driver mutation in the tumor cells and potentially sensitize the immune system to target tumors.
The study will enroll up to 20 patients with advanced melanoma and activating mutations in the BRAF gene for the local administration of talimogene laherparepvec in conjunction with oral therapy with dabrafenib and trametinib, to describe the safety and tolerability of this combination.
Talimogene laherparepvec will be administered by intralesional injection into injectable cutaneous, subcutaneous, or nodal lesions with or without image ultrasound guidance. Talimogene laherparepvec will not be administered into any visceral organ or mucosal membrane lesions. The initial dose of talimogene laherparepvec is up to 4.0 mL of 106 plaque forming units (PFU)/mL. Subsequent doses of talimogene laherparepvec are up to 4.0 mL of 108 PFU/mL. The second dose of talimogene laherparepvec (the first dose of the 108 PFU formulation), will be administered at least 21 days following the initial dose. Subsequent doses will be given approximately every 2 weeks.
Dabrafenib at a dose of 150mg will be self-administered orally twice per day. Trametinib at a dose 2mg will be self-administered orally once per day.
Subjects will be evaluated by physical exam at the beginning of Cycle 1 (Week 1), Cycle 2 (Week 4), Cycle 3 (Week 6), Cycle 4 (Week 8), and every two cycles thereafter. Subjects will be evaluated for dose-limiting toxicities (defined in protocol) at Cycle 2 (Week 4), Cycle 3 (Week 6), and Cycle 4 (Week 8). Efficacy evaluation will be performed by tumor measurements using clinical assessment, CT or PET/CT every 4 cycles with the first non-baseline measurement prior to Cycle 4. Tumor response will be evaluated using RECIST 1.1. Adverse events will be recorded and graded using the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0). Other safety assessments will include clinical laboratory values and physical exam findings. Reporting of adverse events, serious adverse events, and documentation of concomitant medications will occur as needed and at every cycle. Biopsy of a melanoma lesion (preferably uninjected) should occur at least one day prior to Cycle 4 (Week 8). Blood for biomarker analysis will be obtained immediately prior to the on-treatment biopsy, or if the on-treatment biopsy cannot be performed, immediately prior to Cycle 4 (Week 8).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Phase 1b single arm single dose level|
|Masking:||None (Open Label)|
|Masking Description:||No masking|
|Official Title:||A Phase 1b Trial of Talimogene Laherparepvec in Combination With Dabrafenib and Trametinib in Advanced Melanoma With an Activating BRAF Mutation|
|Actual Study Start Date :||June 25, 2017|
|Estimated Primary Completion Date :||June 30, 2020|
|Estimated Study Completion Date :||June 30, 2021|
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
Up to 4mL administered on C1D1 intratumorally
Other Name: Imlygic
Drug: Talimogene Laherparep 100 Mil Pfu/Ml 1Ml
Up to 4 ML administered on Week 4 Day 1 and every 2 weeks thereafter
Other Name: Imlygic
150mg PO qday
Other Name: Tafinlar
2mg PO qday
Other Name: Mekinist
- Rate of Dose Limiting Toxicities (DLT) [ Time Frame: 2 years ]Number of DLT seen in the subject population
- Progression Free Survival [ Time Frame: 4 years ]per RECIST 1.1
- Objective Response Rate [ Time Frame: 4 years ]per RECIST 1.1
- Change in tumor burden [ Time Frame: 4 years ]Best change in tumor diameters
- Time to Response [ Time Frame: 4 years ]In responding patients, time from first dose to achieving objective response
- Duration of Response [ Time Frame: 4 years ]In responding patients, time from first evidence of objective response until progression or end of study
- Lesion-level objective response [ Time Frame: 4 years ]Change in diameters of individual lesions
- Biomarker analysis [ Time Frame: 4 years ]Exploratory analysis including number of participants with changes in CD8+ tumor infiltrating lymphocytes between pre-study and on-study biopsies
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03088176
|Contact: Ari VanderWalde, MD||901-683-0055 ext email@example.com|
|Contact: Curry Luttrell||901-683-0055 ext firstname.lastname@example.org|