scholarly journals Talimogene laherparepvec upregulates immune-cell populations in non-injected lesions: findings from a phase II, multicenter, open-label study in patients with stage IIIB–IVM1c melanoma

2021 ◽  
Vol 9 (3) ◽  
pp. e001621
Author(s):  
Josep Malvehy ◽  
Igor Samoylenko ◽  
Dirk Schadendorf ◽  
Ralf Gutzmer ◽  
Jean-Jacques Grob ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Density ◽  
Phase Ii ◽  
Response Rate ◽  
Objective Response ◽  
Stage Iiib ◽  
Talimogene Laherparepvec ◽  
Durable Response ◽  
Programmed Death

BackgroundTalimogene laherparepvec (T-VEC), an oncolytic virus, was designed to selectively replicate in and lyse tumor cells, releasing tumor-derived antigen to stimulate a tumor-specific immune response.MethodsIn this phase II study in patients with unresectable stage IIIB–IV melanoma, we evaluated non-injected lesions to establish whether baseline or change in intratumoral CD8+ T-cell density (determined using immunohistochemistry) correlated with T-VEC clinical response.ResultsOf 112 enrolled patients, 111 received ≥1 dose of T-VEC. After a median follow-up of 108.0 weeks, objective/complete response rates were 28%/14% in the overall population and 32%/18% in patients with stage IIIB–IVM1a disease. No unexpected toxicity occurred. Baseline and week 6 change from baseline CD8+ T-cell density results were available for 91 and 65 patients, respectively. Neither baseline nor change in CD8+ T-cell density correlated with objective response rate, changes in tumor burden, duration of response or durable response rate. However, a 2.4-fold median increase in CD8+ T-cell density in non-injected lesions from baseline to week 6 was observed. In exploratory analyses, multiparameter immunofluorescence showed that after treatment there was an increase in the proportion of infiltrating CD8+ T-cells expressing granzyme B and checkpoint markers (programmed death-1, programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen-4) in non-injected lesions, together with an increase in helper T-cells. Consistent with T-cell infiltrate, we observed an increase in the adaptive resistance marker PD-L1 in non-injected lesions.ConclusionsThis study indicates that T-VEC induces systemic immune activity and alters the tumor microenvironment in a way that will likely enhance the effects of other immunotherapy agents in combination therapy.Trial registration numberNCT02366195.

Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma

2015 ◽  
Vol 33 (25) ◽  
pp. 2780-2788 ◽  
Author(s):  
Robert H.I. Andtbacka ◽  
Howard L. Kaufman ◽  
Frances Collichio ◽  
Thomas Amatruda ◽  
Neil Senzer ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Stage Iiib ◽  
Phase Iii ◽  
Talimogene Laherparepvec ◽  
Durable Response ◽  
Overall Response ◽  
Gm Csf ◽  
Oncolytic Immunotherapy

Purpose Talimogene laherparepvec (T-VEC) is a herpes simplex virus type 1–derived oncolytic immunotherapy designed to selectively replicate within tumors and produce granulocyte macrophage colony-stimulating factor (GM-CSF) to enhance systemic antitumor immune responses. T-VEC was compared with GM-CSF in patients with unresected stage IIIB to IV melanoma in a randomized open-label phase III trial. Patients and Methods Patients with injectable melanoma that was not surgically resectable were randomly assigned at a two-to-one ratio to intralesional T-VEC or subcutaneous GM-CSF. The primary end point was durable response rate (DRR; objective response lasting continuously ≥ 6 months) per independent assessment. Key secondary end points included overall survival (OS) and overall response rate. Results Among 436 patients randomly assigned, DRR was significantly higher with T-VEC (16.3%; 95% CI, 12.1% to 20.5%) than GM-CSF (2.1%; 95% CI, 0% to 4.5%]; odds ratio, 8.9; P < .001). Overall response rate was also higher in the T-VEC arm (26.4%; 95% CI, 21.4% to 31.5% v 5.7%; 95% CI, 1.9% to 9.5%). Median OS was 23.3 months (95% CI, 19.5 to 29.6 months) with T-VEC and 18.9 months (95% CI, 16.0 to 23.7 months) with GM-CSF (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P = .051). T-VEC efficacy was most pronounced in patients with stage IIIB, IIIC, or IVM1a disease and in patients with treatment-naive disease. The most common adverse events (AEs) with T-VEC were fatigue, chills, and pyrexia. The only grade 3 or 4 AE occurring in ≥ 2% of T-VEC–treated patients was cellulitis (2.1%). No fatal treatment-related AEs occurred. Conclusion T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial. T-VEC was well tolerated and resulted in a higher DRR (P < .001) and longer median OS (P = .051), particularly in untreated patients or those with stage IIIB, IIIC, or IVM1a disease. T-VEC represents a novel potential therapy for patients with metastatic melanoma.

Differentiated activity profile for the PD-1 inhibitor balstilimab.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5529-5529
Author(s):  
Cailin Joyce ◽  
Dhan Chand ◽  
Benjamin Duckless ◽  
Manuel Hidalgo ◽  
Joseph Elan Grossman ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
Culture System ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Activity Profile ◽  
Double Positive ◽  
Programmed Death

5529 Background: The development and clinical application of immune checkpoint inhibitors has transformed the therapeutic landscape for cancer treatment in recent years. Balstilimab (AGEN2034) is a fully human, monoclonal IgG4 antibody that binds with high affinity to programmed death 1 (PD-1), thus preventing the interaction between this receptor and its ligands programmed death ligand 1 and 2 (PD-L1, PD-L2). Emerging evidence suggests that balstilimab exhibits a differentiated activity profile compared to currently approved anti-PD-1 agents, including pembrolizumab and nivolumab. Methods: Balstilimab as monotherapy was evaluated in a large phase 2 study in patients (pts) with recurrent/metastatic cervical cancer who had relapsed after a platinum-based treatment regimen for advanced disease. Pts were dosed at 3 mg/kg once every 2 weeks for up to 24 months and antitumor activity was assessed using RECIST v1.1. The tumor cell killing activity of balstilimab was evaluated preclinically in a human co-culture system of (1) primary T cells engineered to recognize NY-ESO-1 and (2) NY-ESO-1+ cancer cell lines, including PD-L1 and/or PD-L2-deficient engineered lines. The co-culture system was maintained for ̃ two weeks to drive partial T cell exhaustion; a state where cytotoxicity is compromised but recoverable with PD-1 blockade. Cytotoxicity of these partially exhausted T cells was quantified against PD-L1/L2 double positive, single positive, or double negative cancer cells in the presence or absence of PD-(L)1 antibodies. Results: In the second-line treatment setting for pts with advanced cervical cancer, balstilimab showed a numerically higher objective response rate (ORR) in subjects with PD-L1+, squamous cell carcinoma (SCC) tumors (21%, 95% CI, 12.7-32.6%) than those reported for pembrolizumab. Unlike pembrolizumab, balstilimab showed activity in PD-L1(-) pts, and irrespective of tumor histology (ORR 7.9%, 95% CI, 2.7-20.8%). Despite lower overall PD-L1 positivity compared to SCC (41.7 v 72.9%), an ORR of 12.5% (95% CI, 5.9-24.7%) was observed in the subset of pts with a poorer prognosis, those with cervical adenocarcinoma. Concordant with clinical observations, balstilimab demonstrated superior rescue of antigen-specific T cell cytotoxicity in vitro relative to pembrolizumab, nivolumab, or atezolizumab. Balstilimab also induced cytotoxicity against PD-L1 and/or PD-L2 deficient target cancer cells. Conclusions: Taken together, these data suggest functional differentiation of balstilimab from other PD-1 inhibitors with potentially important implications for extending the therapeutic reach of anti-PD-1 therapy. Investigation of the underlying mechanistic basis for these findings is ongoing. Clinical trial information: NCT03104699.

Design and rationale of MASTERKEY-115 phase II trial of talimogene laherparepvec (T-VEC) with pembrolizumab (pembro) in patients with advanced melanoma who progressed on prior anti-programmed cell death-1 (anti-PD-1) therapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS10079-TPS10079
Author(s):  
Jason Alan Chesney ◽  
Mohammed M. Milhem ◽  
Marya F. Chaney ◽  
Priya Gokani ◽  
Wendy Snyder ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Objective Response Rate ◽  
Cell Activation ◽  
Response Rate ◽  
Objective Response ◽  
Cell Activity ◽  
Advanced Melanoma ◽  
Durable Response ◽  
Metastatic Setting

TPS10079 Background: Treatment options are limited for patients with advanced metastatic or unresectable melanoma, especially after anti-PD-1 failure. T-VEC is an intralesional oncolytic viral immunotherapy designed to selectively replicate in tumor cells and induce local and systemic antitumor response. Pembro promotes T cell activity by blocking PD-1 receptors. Combining T-VEC and pembro may produce robust antitumor activity by increasing T cell activation and blocking T cell inhibition, with a tolerable safety profile. The MASTERKEY-115 trial will evaluate safety and efficacy of T-VEC combined with pembro in patients with advanced melanoma who experienced progressive disease (PD) on prior anti-PD-1 therapy. Methods: NCT04068181 is a phase 2, open-label, single-arm, multicenter trial of T-VEC with pembro in patients with advanced melanoma and PD on prior anti-PD-1. The study is expected to enroll approximately 100 patients and comprises 4 cohorts. Cohorts 1 and 2 will receive anti-PD-1 in a locally recurrent or metastatic setting and experienced PD within 12 weeks of the last anti-PD-1 dose (Cohort 1: PD or stable disease prior to confirmed PD; Cohort 2: complete or partial response prior to confirmed PD). Cohorts 3 and 4 will receive adjuvant anti-PD-1 and were disease-free for < 6 months (Cohort 3) or ≥ 6 months (Cohort 4) prior to confirmed PD. Enrollment criteria include adults with histologically confirmed unresectable or metastatic stage IIIB–IVM1d melanoma, measurable and injectable disease, ECOG PS 0-1, and prior anti-PD-1 (≥ 2-3 consecutive cycles within 8 weeks, immediate prior treatment before enrollment). The primary endpoint is objective response rate per modified RECIST. Key secondary endpoints assess efficacy (objective response rate, best overall response, complete response rate, response duration, durable response rate, disease control rate, progression-free survival, overall survival), safety (incidence of treatment-emergent and treatment-related adverse events, abnormal laboratory tests), and time to subsequent anticancer therapy. The study began enrolling patients in January 2020 and enrollment is ongoing. Clinical trial information: NCT04068181.

scholarly journals Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma

2018 ◽  
Vol 36 (17) ◽  
pp. 1658-1667 ◽  
Author(s):  
Jason Chesney ◽  
Igor Puzanov ◽  
Frances Collichio ◽  
Parminder Singh ◽  
Mohammed M. Milhem ◽  
...  
Keyword(s):  
Phase Ii ◽  
Objective Response Rate ◽  
Response Rate ◽  
Phase Ii Study ◽  
Objective Response ◽  
Talimogene Laherparepvec ◽  
Open Label ◽  
Prior Therapy ◽  
End Point ◽  
Open Label Phase

Purpose We evaluated the combination of talimogene laherparepvec plus ipilimumab versus ipilimumab alone in patients with advanced melanoma in a phase II study. To our knowledge, this was the first randomized trial to evaluate addition of an oncolytic virus to a checkpoint inhibitor. Methods Patients with unresectable stages IIIB to IV melanoma, with no more than one prior therapy if BRAF wild-type, no more than two prior therapies if BRAF mutant, measurable/injectable disease, and without symptomatic autoimmunity or clinically significant immunosuppression were randomly assigned 1:1 to receive talimogene laherparepvec plus ipilimumab or ipilimumab alone. Talimogene laherparepvec treatment began in week 1 (first dose, ≤ 4 mL × 106 plaque-forming units/mL; after 3 weeks, ≤ 4 mL × 108 plaque-forming units/mL every 2 weeks). Ipilimumab (3 mg/kg every 3 weeks; up to four doses) began week 1 in the ipilimumab alone arm and week 6 in the combination arm. The primary end point was objective response rate evaluated by investigators per immune-related response criteria. Results One hundred ninety-eight patients were randomly assigned to talimogene laherparepvec plus ipilimumab (n = 98), or ipilimumab alone (n = 100). Thirty-eight patients (39%) in the combination arm and 18 patients (18%) in the ipilimumab arm had an objective response (odds ratio, 2.9; 95% CI, 1.5 to 5.5; P = .002). Responses were not limited to injected lesions; visceral lesion decreases were observed in 52% of patients in the combination arm and 23% of patients in the ipilimumab arm. Frequently occurring adverse events (AEs) included fatigue (combination, 59%; ipilimumab alone, 42%), chills (combination, 53%; ipilimumab alone, 3%), and diarrhea (combination, 42%; ipilimumab alone, 35%). Incidence of grade ≥ 3 AEs was 45% and 35%, respectively. Three patients in the combination arm had fatal AEs; none were treatment related. Conclusion The study met its primary end point; the objective response rate was significantly higher with talimogene laherparepvec plus ipilimumab versus ipilimumab alone. These data indicate that the combination has greater antitumor activity without additional safety concerns versus ipilimumab.

scholarly journals Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma

2016 ◽  
Vol 34 (22) ◽  
pp. 2619-2626 ◽  
Author(s):  
Igor Puzanov ◽  
Mohammed M. Milhem ◽  
David Minor ◽  
Omid Hamid ◽  
Ai Li ◽  
...  
Keyword(s):  
Objective Response Rate ◽  
Response Rate ◽  
Cytotoxic T Lymphocyte ◽  
Objective Response ◽  
Progression Free Survival ◽  
Talimogene Laherparepvec ◽  
Duration Of Treatment ◽  
Open Label ◽  
Durable Response ◽  
Grade 3

Purpose Combining immunotherapeutic agents with different mechanisms of action may enhance efficacy. We describe the safety and efficacy of talimogene laherparepvec (T-VEC; an oncolytic virus) in combination with ipilimumab (a cytotoxic T-lymphocyte–associated antigen 4 checkpoint inhibitor) in patients with advanced melanoma. Methods In this open-label, multicenter, phase Ib trial of T-VEC in combination with ipilimumab, T-VEC was administered intratumorally in week 1 (106 plaque-forming units/mL), then in week 4 and every 2 weeks thereafter (108 plaque-forming units/mL). Ipilimumab (3 mg/kg) was administered intravenously every 3 weeks for four infusions, beginning in week 6. The primary end point was incidence of dose-limiting toxicities. Secondary end points were objective response rate by immune-related response criteria and safety. Results Median duration of treatment with T-VEC was 13.3 weeks (range, 2.0 to 95.4 weeks). Median follow-up time for survival analysis was 20.0 months (1.0 to 25.4 months). Nineteen patients were included in the safety analysis. No dose-limiting toxicities occurred, and no new safety signals were detected. Grade 3/4 treatment-related adverse events (AEs) were seen in 26.3% of patients; 15.8% had AEs attributed to T-VEC, and 21.1% had AEs attributed to ipilimumab. The objective response rate was 50%, and 44% of patients had a durable response lasting ≥ 6 months. Eighteen-month progression-free survival was 50%; 18-month overall survival was 67%. Conclusion T-VEC with ipilimumab had a tolerable safety profile, and the combination appeared to have greater efficacy than either T-VEC or ipilimumab monotherapy.

430 A phase II study of nivolumab + BMS-986016 (relatlimab) in patients with metastatic uveal melanoma(UM) (CA224–094)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A455-A455
Author(s):  
Jose Lutzky ◽  
Jose Lutzky ◽  
Lynn Feun ◽  
William Harbour
Keyword(s):  
T Cells ◽  
T Cell ◽  
Uveal Melanoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Type I ◽  
List Type ◽  
Tumor Escape ◽  
Potential Candidate

BackgroundFifty percent of patients with uveal melanoma (UM) develop metastatic disease, surviving 6–12 months from metastatic diagnosis. Liver-directed therapies, immunotherapy, targeted therapy and chemotherapy have limited activity. Lymphocyte activation gene 3(LAG-3) is an immune checkpoint receptor associated with decreased T-cell effector function and tumor escape. Preclinical models have shown that dual inhibition of LAG-3 and PD-1 blockade generates synergistic anti-tumor activity.1 In uveal melanoma, CD8+ T cells express the checkpoint receptor LAG3 to a greater extent than PD1 or CTLA4.2 3 This recent discovery nominates LAG3 as a potential candidate for checkpoint inhibitor immunotherapy in UM.MethodsThis is an open-label, single arm, single site investigator-initiated phase II study. Based on Simon two-stage minimax design, 13 patients will be enrolled in Stage 1. If at least one response is noted, the study will proceed to Stage 2 and enroll additional 14 patients. The null hypothesis will be rejected if 4 or more responses are observed among 27 patients. This design achieves 5% type I error and 80% power when the true ORR is 20%.Main eligibility criteria includes patients with biopsy proven metastatic uveal melanoma, previously untreated with PD-1, CTLA-4 and/or LAG-3 blocking antibodies and in good performance status.Enrolled patients will be treated in the outpatient setting. Nivolumab 480 mg will be mixed in the same bag with relatlimab 160 mg and administered intravenously over 60 minutes every 4 weeks until disease progression or intolerable toxicity for up to 24 months.The primary endpoint is best objective response rate (ORR). Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), median duration of response (mDOR), and adverse events (AEs). Correlative studies will evaluate pre- and post-treatment characteristics of T cells in the tumor microenvironment and blood.ResultsN/AConclusionsN/AEthics ApprovalThe study was approved by the University of Miami Sylvester Cancer Center PRMC #20200847ConsentN/AReferencesWoo SR, Turnis ME, Goldberg MV, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res 2012. 72(4): p. 917–27.Durante MA, Rodriguez DA, Kurtenbach S, et al. Single-cell analysis reveals new evolutionary complexity in uveal melanoma. Nat Commun2020;11(1):496. Published 2020 Jan 24. doi:10.1038/s41467-019-14256-1Karlsson J, Nilsson LM, Mitra S, et al. Molecular profiling of driver events in metastatic uveal melanoma. Nat Commun2020;11(1):1894. Published 2020 Apr 20. doi:10.1038/s41467-020-15606-0

scholarly journals Good Tolerance and Durable Remission for Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy in Refractory/Relapsed Mantle Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2818-2818 ◽  
Author(s):  
Shiguang Ye ◽  
Lili Zhou ◽  
Shaoguang Li ◽  
Ping Li ◽  
Aibin Liang
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Objective Response ◽  
The Other ◽  
Durable Response ◽  
Car T ◽  
Mantle Cell

Mantle cell lymphoma (MCL) is one subtype of the B cell non-Hodgkin lymphomas (NHL) and has a distinguash course. Despite all efforts, MCL is nearly incurable that refractory or relapse(r/r) course will occur in almost all patients. Due to the rapid development of chemotherapy resistance, it is difficult to treat r/r MCL. A number of treatment regimens have been evaluated with various degrees of success. Cellular immunotherapy has the potential to lead significant and sustained clinical remissions in lymphoma patients, in which modification of T cells with chimeric antigen receptors (CARs) is a powerful regimen. T cells containing CARs with costimulatory domains show better activity against tumor cells. We conducted a clinical trial testing a "second-generation" CD19-specific CAR with 4-1BB costimulatory domains in patients with r/r MCL. Six patients with r/r MCL were enrolled and all were received T-cell infusions. The age of patients ranged from 52 to 81 years old. Five patients were male and one patient was female. Five patients had stage IV MCL with bone marrow involvement and one patient was stage II. Four patients had received more than 3 lines regimens and two patients had received first-line chemotherapy regimen. Four patients received FC regimen before CAR-T infusion and two patients were not received fludarabine due to age ≥80 years old. Treatment was well tolerated, two patients developed transient infusion reaction. No patients have grade 3-4 Cytokine Release Syndrome (CRS). Three patients have grade 2 CRS and two patients have grade 1 CRS. Objective response rate is 66.67%. One patient achieves complete remission(CR) and three patients have partial remission(PR). The response of the other two patients is stable disease(SD). The patient who has CR response has remained progression-free for 36 months and is still being followed up. Two patients who have PR response have progressed in 3 months and the other one has durable response for 7 months. In the patients who has response, the peak of fever appears at approximately day 10 after CAR-T infusion, moreover interleukin(IL)6,IL2αand interferon(IFN)-γ almost reaches the peak on the day 14. In conclusion, adoptive immunotherapy with CD19-specific T cells was well tolerated and was associated with antitumor activity. Further large-sample and multicenter studies are needed to fully evaluate this strategy for such patients. Disclosures No relevant conflicts of interest to declare.

Product characteristics associated with in vivo expansion of anti-CD19 CAR T cells in patients treated with axicabtagene ciloleucel (axi-cel).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3023-3023 ◽  
Author(s):  
Frederick Lundry Locke ◽  
John Rossi ◽  
Sattva Swarup Neelapu ◽  
Allen Xue ◽  
Marc Better ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Response Rate ◽  
Objective Response ◽  
Blood Levels ◽  
Product Characteristics ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T

3023 Background: Axi-cel (formerly KTE-C19) is an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy. ZUMA-1 is a multicenter, registrational trial of axi-cel in patients (pts) with refractory aggressive non-Hodgkin lymphoma. In a prespecified interim analysis, ZUMA-1 met its primary endpoint, with a 76% objective response rate and a 47% complete response rate ( Blood 2016;128:LBA-6). Post-treatment CAR T cell blood levels were associated with objective response. Here, we describe novel associations between product characteristics and CAR T cell levels in pts. Methods: CAR T cell characteristics in axi-cel produced from 62 pts were analyzed by flow cytometry and modeled against CAR T cell levels. In vivo CAR T cell levels were measured by qPCR. T cell expansion during production (fold expansion/total days in culture) was compared with CAR T cell blood levels, using a partition analysis with expansion rates of ≥1 vs < 1. Wilcoxon 2-sample test and linear regression were used. Results: Axi-cel contained CCR7+ T cells (median, 42%; range, 15–73%), with naïve (CD45RA+/CCR7+; median, 12%; range, 1–57%), central memory (CD45RA−/CCR7+; median, 29%; range, 12–49%) phenotypes, and more differentiated CCR7− effector memory and effector T cells. On infusion, CAR T cells expanded rapidly, reaching peak levels within 2 weeks (median, 43 cells/μL; range, 1–1513), and were also measurable in all pts at 1 month (median, 2 cells/μL; range, 0.03–89). The CCR7+/CCR7− T cell ratio in axi-cel associated positively with peak ( P =0.001) and cumulative ( P =0.003) CAR T cell levels through 1 month. Axi-cel lots that expanded more rapidly during production (≥1.0-fold/d; n = 18/62) associated with higher cumulative levels of CAR T cells ( P =0.03). Other product characteristics, eg, CD4/CD8 ratio or number of infused T cells, were not significantly associated with CAR T cell blood levels. Conclusions: An association was observed between CAR T cell expansion in vivo and both the T cell growth rate during production and product cell phenotype pretreatment. A key attribute of axi-cel product was the presence of CCR7+ naïve/central memory T cells, without upfront T cell subset selection. Clinical trial information: NCT02348216.

Rate of complete and durable responses of intralesional therapy with talimogene laherparepvec for stage IIIB-IVM1a melanoma and association with tumor load.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22089-e22089
Author(s):  
Emma H.A. Stahlie ◽  
Viola Franke ◽  
Charlotte L. Zuur ◽  
Willem M.C. Klop ◽  
Bernies Van Der Hiel ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Prediction Model ◽  
Tumor Size ◽  
Response Rate ◽  
Complete Response ◽  
Stage Iiib ◽  
Talimogene Laherparepvec ◽  
Durable Response ◽  
Size Type

e22089 Background: Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex type 1 virus, which is used as an oncolytic immunotherapy in stage IIIB-IVM1a melanoma patients. It is known to be an effective therapy for injectable cutaneous, subcutaneous and nodal melanoma lesions, as approved by the European Medicines Agency (EMA). Combination therapy is not yet approved by EMA pending the results of the phase 3 Masterkey-265 trial. The objective of the current study was to identify prognostic factors for achieving a complete response (CR) that can be used to select patients for treatment with T-VEC monotherapy. Methods: Patients with stage IIIB-IVM1a melanoma, treated with T-VEC at the Netherlands Cancer Institute between 2016-12 and 2019-05 with a follow-up time > 6 months, were included. Data was collected on baseline characteristics, responses and adverse events (AEs). Durable response rate (DRR) was defined as the percent of patients with a CR or partial response (PR) maintained continuously > 6 months. Univariable analyses were conducted and a prediction model was developed to identify prognostic factors associated with complete response. Results: For this study, a total of 71 patients were included with a median follow-up of 16.1 months. The median age was 70 years (range: 35-90). As best response, 47 patients (66%) had a CR and 10 patients (14%) had a PR, resulting in an overall response rate of 80%. Twenty-one patients (30%) stopped treatment because of progressive disease and sixteen patients (23%) developed a recurrence during follow-up after achieving a PR or CR. Median duration of CR was 11 months. The durable response rate was 42%. Grade 1-2 AEs occurred in almost every patient. Tumor size, type of metastases, previous treatment with systemic therapy and stage (8Th AJCC) were independent prognostic factors for achieving a CR and for progression-free survival. Achieving a CR was associated with a reduced risk of death. The prediction model includes tumor size, type of metastases (only cutaneous vs. subcutaneous (+/- cutaneous) vs. nodal (+/- cutaneous/subcutaneous)) and number of lesions as predictors. Conclusions: This study shows that intralesional T-VEC monotherapy for stage IIIB-IVM1a melanoma is able to achieve high complete and durable response rates. The prediction model shows that use of T-VEC in patients with less tumor burden is associated with better outcomes, suggesting T-VEC should perhaps be used earlier in the course of the disease.

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