TIL + Pembrolizumab for Melanoma
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byStephanie L Goff, M.D.
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Steroids, Investigational agents
Disqualifiers: Pregnancy, Immunodeficiency, Infections, Autoimmune, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?Background:
Cell therapy is an experimental cancer therapy. It takes young tumor infiltrating lymphocytes (Young TIL) cells from a person s tumors and grows them in a lab. Then they are returned to the person. Researchers think adding the drug pembrolizumab might make the therapy more effective.
Objective:
To test if adding pembrolizumab to cell therapy is safe and effective to shrink melanoma tumors.
Eligibility:
People ages 18-72 years with metastatic melanoma OF THE SKIN
Design:
Participants will be screened with:
Physical exam
CT, MRI, or PET scans
X-rays
Heart and lung function tests if indicated
Blood and urine tests
Before treatment, participants will have:
A piece of tumor taken from a biopsy or during surgery in order to grow TIL cells
Leukapheresis: Blood flows through a needle in one arm and into a machine that removes white blood cells.
The rest of the blood returns through a needle in the other arm.
An IV catheter placed in the chest for getting TIL cells, aldesleukin, and pembrolizumab (if assigned)
Participants will stay in the hospital for treatment. This includes:
Daily chemotherapy for 1 week
For some participants, pembrolizumab infusion 1 day after chemotherapy
TIL cell infusion 2-4 days after chemotherapy, then aldesleukin infusion every 8 hours for up to 12 doses
Filgrastim injections to help restore your blood counts
Recovery for 1-3 weeks
After treatment, participants will:
Take an antibiotic and an antiviral for at least 6 months, as applicable
If assigned, have pembrolizumab treatment every 3 weeks for 3 more doses. They may have another round.
Have 2-day follow-up visits every 1-3 months for 1 year and then every 6 months
Do I need to stop my current medications to join the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients must have completed any prior systemic therapy at the time of enrollment, which might imply stopping certain treatments. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the treatment TIL + Pembrolizumab for Melanoma?
Research shows that tumor-infiltrating lymphocytes (TILs) and pembrolizumab, a drug that blocks a protein called PD-1, can help the immune system fight cancer. While studies specifically on melanoma are limited, similar treatments have shown promise in other cancers, suggesting potential benefits for melanoma as well.
12345Is the combination of TIL and Pembrolizumab safe for humans?
Pembrolizumab, also known as KEYTRUDA, has been shown to have a generally acceptable safety profile in various studies, including those for melanoma and multiple myeloma. Some side effects have been reported, such as diarrhea and lung inflammation, but they were manageable and resolved without lasting effects.
34678How is the TIL + Pembrolizumab treatment for melanoma different from other treatments?
The TIL + Pembrolizumab treatment is unique because it combines tumor-infiltrating lymphocytes (TIL), which are immune cells extracted from the patient's own tumor, with pembrolizumab, a drug that helps the immune system attack cancer cells. This combination aims to enhance the body's immune response against melanoma, offering a novel approach compared to standard treatments that typically involve only drugs like pembrolizumab.
478910Eligibility Criteria
Adults aged 18-70 with metastatic melanoma of the skin, who have had at least one prior treatment. Eligible participants may have up to three small, stable brain tumors and must practice birth control. Excluded are those with severe allergies, immune deficiencies, active infections or major illnesses, pregnant or breastfeeding women, and anyone on systemic steroids.Inclusion Criteria
Measurable metastatic melanoma with at least one lesion that is resectable for TIL generation
Confirmation of diagnosis of metastatic melanoma by the Laboratory of Pathology of NCI
Patients must have received at least one prior therapy for metastatic melanoma
+19 more
Exclusion Criteria
Patients who are receiving any other investigational agents
Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant
Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease)
+9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Multiple visits for physical exams, imaging, and lab tests
Treatment
Participants receive a non-myeloablative lymphodepleting regimen, TIL infusion, and high-dose IL-2. Some participants also receive pembrolizumab.
4-6 weeks
Inpatient stay for chemotherapy, TIL infusion, and IL-2 administration
Recovery
Participants recover from treatment and receive supportive care including filgrastim injections.
1-3 weeks
Inpatient stay for recovery and monitoring
Follow-up
Participants are monitored for safety and effectiveness after treatment, with pembrolizumab administered every 3 weeks for 3 more doses if applicable.
1 year
2-day follow-up visits every 1-3 months
Long-term Follow-up
Participants continue to be monitored for progression-free survival and overall survival.
2 years
Follow-up visits every 6 months
Participant Groups
The trial is testing if adding pembrolizumab (an immunotherapy drug) to adoptive cell therapy using tumor infiltrating lymphocytes (TIL) plus IL-2 is safe and effective for shrinking melanoma tumors. Participants will receive chemotherapy followed by TIL infusion and possibly pembrolizumab.
3Treatment groups
Experimental Treatment
Group I: 3/ACT TIL (Pembro contraindicated)Experimental Treatment4 Interventions
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + young TIL + highdose aldesleukin (IL-2)
Group II: 2/ACT TIL + PembroExperimental Treatment5 Interventions
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2) + pembrolizumab
Group III: 1/ACT TILExperimental Treatment4 Interventions
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine +young TIL + highdose aldesleukin (IL-2)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, MD
National Institutes of Health Clinical CenterBethesda, MD
Loading ...
Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Prognostic significance of tumor infiltrating lymphocytes on first-line pembrolizumab efficacy in advanced non-small cell lung cancer. [2023]Tumor-infiltrating lymphocytes (TILs) in the tumor and stroma are expected to accurately predict the efficacy of programmed death-1 (PD-1) blockade therapy. However, little is known about the prognostic significance of TILs in first-line PD-1 therapy. We assessed TILs in patients with advanced or metastatic non-small cell lung cancer (NSCLC) treated with pembrolizumab in the palliative setting.
Prognostic Significance of Primary Tumor-Infiltrating Lymphocytes in a Contemporary Melanoma Cohort. [2023]The prognostic impact of tumor-infiltrating lymphocytes (TILs) on outcomes and treatment efficacy for patients with melanoma in the contemporary era remains poorly characterized.
TIL in Melanoma-Similar Approaches, Different Results, Unanswered Questions. [2022]Prior treatment with anti-PD-1 and/or BRAF-targeted therapies was associated with limited activity of tumor infiltrating lymphocytes (TIL) in metastatic melanoma. Recent insights into mechanisms of action for TIL and anti-PD-1 provide the foundation for understanding differences in outcomes in different trials or populations, and a roadmap for developing improved products. See related article by Seitter et al., p. 5289.
Exposure to anti-PD-1 causes functional differences in tumor-infiltrating lymphocytes in rare solid tumors. [2020]The pervasive use of therapeutic antibodies targeting programmed cell death protein 1 (PD-1) to boost anti-tumor immunity has positioned this approach to become the standard-of-care for some solid tumor malignancies. However, little is known as to how blockade of PD-1 may alter the function or phenotype of tumor-infiltrating lymphocytes (TIL). We used our ongoing Phase II clinical trial of pembrolizumab for patients with rare solid tumors from various types (NCT02721732) with matched core biopsies taken at baseline and after initial dose of anti-PD-1 (15-21 days post-dose) to elucidate this question. One fresh core needle biopsy was used to propagate TIL ex vivo to analyze phenotype and function using flow cytometry in both CD8+ and CD4+ TIL populations. An enriched CTLA-4 expression in the CD4+ TIL population was observed in TIL expanded from the on-treatment samples compared to TIL expanded from the matched baseline (n = 22, p = 0.0007) but was not observed in patients who experienced tumor regression. Impact on functionality was evaluated by measuring secretion of 65 soluble factors by expanded TIL from 26 patients at baseline and on-treatment. The CD8+ TIL population demonstrated a diminished cytokine secretion profile post-pembrolizumab. Overall, our study assesses the ramifications of one dose of anti-PD-1 on TIL in rare solid tumor types.
CD69 on Tumor-Infiltrating Cells Correlates With Neuroblastoma Suppression by Simultaneous PD-1 and PD-L1 Blockade. [2023]Tumor-infiltrating cells play an important role in tumor immunology, and tumor-infiltrating lymphocytes (TILs) are critical in antitumor reaction related to immune checkpoint inhibition targeting programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1).
Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial. [2020]PD1 expression in CD4+ and CD8+ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8+ effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23.
A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151). [2020]Pembrolizumab shows robust antitumor activity and favorable safety in metastatic melanoma. KEYNOTE-151 evaluated pembrolizumab in Chinese patients, who have more aggressive melanoma subtypes than other populations.
New developments in the management of advanced melanoma - role of pembrolizumab. [2020]Cancer immunotherapy is now recognized to be fundamental in modern oncology, because immune system recruitment may represent a powerful and innovative strategy in cancer therapy. Pembrolizumab, a highly selective humanized monoclonal antibody directly blocking the interaction between programmed cell death-1 expressed by tumor-associated T-cells and its ligand programmed cell death-L1 present on tumor and stromal cells, was recently approved by US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma and disease progression upon ipilimumab and BRAF inhibitor. This review will focus on the clinical development and use of pembrolizumab in the clinical practice and in the management of advanced melanoma.
Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]Pembrolizumab is a fully humanized anti-PD-1 agent currently approved for the treatment of advanced melanoma and pretreated non-small-cell lung cancer (NSCLC).
Real-world experience with pembrolizumab in patients with advanced melanoma: A large retrospective observational study. [2022]Pembrolizumab has been approved in the United States for treating advanced melanoma for >4 years. We examined real-world pembrolizumab use and associated outcomes in US oncology clinical practices, including patients who would not be eligible for clinical trials.Flatiron Health longitudinal database was used to identify adult patients with advanced melanoma initiating ≥1 dose of pembrolizumab from September 4, 2014, through December 31, 2016, with follow-up through December 31, 2017. Patients in any clinical trial during the study period were excluded. Overall survival (OS) and time on treatment from pembrolizumab initiation were analyzed using the Kaplan-Meier (KM) method. Subgroup analyses were conducted to examine OS for several patient characteristics including Eastern Cooperative Oncology Group (ECOG) performance status >1, brain metastases, and corticosteroids before pembrolizumab initiation.Pembrolizumab was administered to 315 (59%), 152 (29%), and 65 (12%) patients as first-, second-, and third-line/later therapy. Median age at pembrolizumab initiation was 68 years (range, 18-84); most patients were male (66%) and white (94%). Of those with available data, 38% had BRAF-mutant melanoma, 21% had elevated lactate dehydrogenase (LDH) level, and 23% had ECOG >1. Overall, 18% had brain metastases, and 23% were prescribed corticosteroids 1), normal (vs elevated) LDH level, and no (vs yes) corticosteroid prescription