Dataset Information

Lifileucel, an Autologous Tumor-Infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non-Small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors.

ABSTRACT: In this phase 2 multicenter study, we evaluated the efficacy and safety of lifileucel (LN-145), an autologous tumor-infiltrating lymphocyte cell therapy, in patients with metastatic non-small cell lung cancer (mNSCLC) who had received prior immunotherapy and progressed on their most recent therapy. The median number of prior systemic therapies was 2 (range, 1-6). Lifileucel was successfully manufactured using tumor tissue from different anatomic sites, predominantly lung. The objective response rate was 21.4% (6/28). Responses occurred in tumors with profiles typically resistant to immunotherapy, such as PD-L1-negative, low tumor mutational burden, and STK11 mutation. Two responses were ongoing at the time of data cutoff, including one complete metabolic response in a PD-L1-negative tumor. Adverse events were generally as expected and manageable. Two patients died of treatment-emergent adverse events: cardiac failure and multiple organ failure. Lifileucel is a potential treatment option for patients with mNSCLC refractory to prior therapy. Significance: Autologous tumor-infiltrating lymphocyte therapy lifileucel was administered to 28 patients with heavily pretreated metastatic non-small cell lung cancer (mNSCLC). Responses were observed in patients with driver mutations, and various tumor mutational burdens and PD-L1 expression, potentially addressing an unmet medical need in patients with mNSCLC refractory to prior therapy. See related commentary by Lotze et al., p. 1366.

SUBMITTER: Schoenfeld AJ

PROVIDER: S-EPMC11294887 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lifileucel, an Autologous Tumor-Infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non-Small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors.

Schoenfeld Adam J AJ Lee Sylvia M SM Doger de Spéville Bernard B Gettinger Scott N SN Häfliger Simon S Sukari Ammar A Papa Sophie S Rodríguez-Moreno Juan F JF Graf Finckenstein Friedrich F Fiaz Rana R Catlett Melissa M Chen Guang G Qi Rongsu R Masteller Emma L EL Gontcharova Viktoria V He Kai K

Cancer discovery 20240801 8

In this phase 2 multicenter study, we evaluated the efficacy and safety of lifileucel (LN-145), an autologous tumor-infiltrating lymphocyte cell therapy, in patients with metastatic non-small cell lung cancer (mNSCLC) who had received prior immunotherapy and progressed on their most recent therapy. The median number of prior systemic therapies was 2 (range, 1-6). Lifileucel was successfully manufactured using tumor tissue from different anatomic sites, predominantly lung. The objective response ...[more]

PMID: 38563600

Similar Datasets

Project description:BackgroundEnrichment of tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment (TME) is a reliable biomarker of immune checkpoint inhibitors (ICI) in non-small cell lung cancer (NSCLC). Phenotyping through computed tomography (CT) radiomics has the overcome the limitations of tissue-based assessment, including for TIL analysis. Here, we assess TIL enrichment objectively using an artificial intelligence-powered TIL analysis in hematoxylin and eosin (H&E) image and analyze its association with quantitative radiomic features (RFs). Clinical significance of the selected RFs is then validated in the independent NSCLC patients who received ICI.MethodsIn the training cohort containing both tumor tissue samples and corresponding CT images obtained within 1 month, we extracted 86 RFs from the CT images. The TIL enrichment score (TILes) was defined as the fraction of tissue area with high intra-tumoral or stromal TIL density divided by the whole TME area, as measured on an H&E slide. From the corresponding CT images, the least absolute shrinkage and selection operator model was then developed using features that were significantly associated with TIL enrichment. The CT model was applied to CT images from the validation cohort, which included NSCLC patients who received ICI monotherapy.ResultsA total of 220 NSCLC samples were included in the training cohort. After filtering the RFs, two features, gray level variance (coefficient 1.71 x 10-3) and large area low gray level emphasis (coefficient -2.48 x 10-5), were included in the model. The two features were both computed from the size-zone matrix, which has strength in reflecting intralesional texture heterogeneity. In the validation cohort, the patients with high predicted TILes (≥ median) had significantly prolonged progression-free survival compared to those with low predicted TILes (median 4.0 months [95% CI 2.2-5.7] versus 2.1 months [95% CI 1.6-3.1], p = 0.002). Patients who experienced a response to ICI or stable disease with ICI had higher predicted TILes compared with the patients who experienced progressive disease as the best response (p = 0.001, p = 0.036, respectively). Predicted TILes was significantly associated with progression-free survival independent of PD-L1 status.ConclusionsIn this CT radiomics model, predicted TILes was significantly associated with ICI outcomes in NSCLC patients. Analyzing TME through radiomics may overcome the limitations of tissue-based analysis and assist clinical decisions regarding ICI.

Project description:Background: Immune checkpoint inhibitors (ICIs) are approved as cancer immunotherapeutic agents for advanced malignant melanoma (MM) in recent years, and nivolumab and ipilimumab are the most widely used ICIs either alone or in combination. However, their efficacy and safety between single and combined ICIs are not clear. This meta-analysis (MA) is aimed to update the efficacy and safety of ICIs by comparing monotherapy and combination therapy in the treatment of advanced MM. Method: We searched PubMed, Embase, EbscoHost and ClinicalTrials.gov for the eligible randomized controlled trials (RCTs) which compared the efficacy and safety of ICIs between a single ICI and combined ICIs. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (AEs). A fixed-effect or random-effects model was adopted depending on the study heterogeneity. Results: A total of nine RCTs were included in this MA. Regarding the efficacy, combined nivolumab and ipilimumab therapy showed statistically significant prolonged OS and PFS with HR 0.65, 95% CI [0.53, 0.79], p <0.0001 and HR 0.48, 95% CI [0.38, 0.60], p<0.0001 respectively. Combination therapy with nivolumab and ipilimumab also showed statistically significant longer ORR than monotherapy; with RR 2.15, 95% CI [1.63, 2.84], p <0.00001. In terms of safety, the incidence of all AEs which include any AEs, high-grade, haematological, gastrointestinal, dermatological, pulmonary, liver and endocrine AEs were significantly lower with monotherapy (either nivolumab or ipilimumab) of ICI compared to combination ICI therapy with a p-value <0.00001 to 0.03. Conclusion: Efficacy of the combined nivolumab and ipilimumab was better than a single ICI, especially in the treatment of advanced MM. Although combination therapy showed better efficacy than monotherapy, monotherapy (either nivolumab or ipilimumab) was safer than combination therapy as it tended to decrease the incidence of most of the treatment-related AEs.

Project description:BackgroundPatients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma.MethodsEligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing practice facility for 22-day lifileucel manufacturing. Patients received a non-myeloablative lymphodepletion regimen, a single lifileucel infusion, and up to six doses of high-dose interleukin-2. The primary endpoint was IRC-assessed ORR (Response Evaluation Criteria in Solid Tumors V.1.1).ResultsThe Full Analysis Set consisted of 153 patients treated with lifileucel, including longer-term follow-up on the 66 patients previously reported. Patients had received a median of 3.0 lines of prior therapy (81.7% received both anti-programmed cell death protein 1 and anti-cytotoxic lymphocyte-associated protein 4) and had high disease burden at baseline (median target lesion sum of diameters (SOD): 97.8 mm; lactate dehydrogenase (LDH) >upper limit of normal: 54.2%). ORR was 31.4% (95% CI: 24.1% to 39.4%), with 8 complete responses and 40 partial responses. Median duration of response was not reached at a median study follow-up of 27.6 months, with 41.7% of the responses maintained for ≥18 months. Median overall survival and progression-free survival were 13.9 and 4.1 months, respectively. Multivariable analyses adjusted for Eastern Cooperative Oncology Group performance status demonstrated that elevated LDH and target lesion SOD >median were independently correlated with ORR (p=0.008); patients with normal LDH and SOD <median had greater likelihood of response than those with either (OR=2.08) or both (OR=4.42) risk factors. The most common grade 3/4 treatment-emergent adverse events (≥30%) were thrombocytopenia (76.9%), anemia (50.0%), and febrile neutropenia (41.7%).ConclusionsInvestigational lifileucel demonstrated clinically meaningful activity in heavily pretreated patients with advanced melanoma and high tumor burden. Durable responses and a favorable safety profile support the potential benefit of one-time lifileucel TIL cell therapy in patients with limited treatment options in ICI-refractory disease.

Dataset Information

Lifileucel, an Autologous Tumor-Infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non-Small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors.

Publications

Lifileucel, an Autologous Tumor-Infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non-Small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets