1488 A multicenter phase 2 trial of lifileucel plus pembrolizumab in patients with checkpoint inhibitor-naive metastatic NSCLC: updated results
Bibliographic record
Abstract
Background Resistance to frontline immune checkpoint inhibitor (ICI) ± chemotherapy presents a challenge in the treatment of metastatic non-small cell lung cancer (NSCLC). Tumor-infiltrating lymphocyte (TIL) cell therapy with lifileucel alone demonstrated an objective response rate (ORR) of 21% in patients with refractory metastatic NSCLC previously treated with an ICI. Integration of TIL cell therapy in frontline regimens may improve long-term outcomes in NSCLC. We report updated efficacy and safety results for lifileucel combined with pembrolizumab in patients with ICI-naive metastatic NSCLC. Methods IOV-COM-202 (NCT03645928) is a global, phase 2, multicenter, multicohort, open-label study. Cohort 3A has enrolled patients with ICI-naive advanced or metastatic NSCLC with disease progression, ≥1 resectable lesion for lifileucel manufacturing, and ≥1 evaluable lesion (by RECIST v1.1). Patients received nonmyeloablative lymphodepletion (cyclophosphamide and fludarabine), followed by a single lifileucel infusion, and ≤6 doses of high-dose interleukin-2 (IL-2). Pembrolizumab was administered once before lymphodepletion and continued after lifileucel up to 2 years. Primary endpoints were ORR and safety (incidence of grade ≥3 TEAEs). Results As of August 12, 2024, 22 patients had been infused with lifileucel. Patients had a median age of 57 years (range, 30–69) and a median of 1 (range, 0–4) lines of prior systemic therapy. PD-L1 tumor proportion score was <1 in 77.3% (n=17), tumor EGFR status was wild-type (wt) in 63.6% (n=14). Common anatomic sites of tumor resection were lung (45.5%) and lymph node (22.7%). Median lifileucel dose was 22.9×109 cells. At a median follow-up of 25.6 months, the ORR (95% CI) in the EGFR-wt subgroup of interest for further studies was 64.3% (35.1%–87.2%). Median DOR in this subgroup was not reached (NR; 95% CI, 3.7 months–NR). Six responses occurred in 11 patients with EGFR-wt PD-L1–negative disease (54.5%). Five patients had durable and ongoing responses at last follow-up, including 3 patients with PD-L1–negative status (figure 1). For the EGFR-mutation post-TKI (n=8) subgroup, the ORR was 12.5%. TEAEs were consistent with underlying disease and known profiles of pembrolizumab, nonmyeloablative lymphodepletion, and IL-2. Most common grade ≥3 nonhematologic TEAEs were hypoxia (54.5%), febrile neutropenia (45.5%), and hypophosphatemia (31.8%). Conclusions In patients with ICI-naive metastatic NSCLC, lifileucel plus pembrolizumab demonstrated robust antitumor activity and durable responses, including in patients with EGFR-wt PD-L1–negative tumors. No new safety signals were observed with lifileucel plus pembrolizumab. These results support further investigation of lifileucel/ICI combination as part of frontline therapy in metastatic NSCLC. Trial Registration NCT03645928. Ethics Approval This study was approved by the institutional review board at each site and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines of the International Conference on Harmonization. All patients provided written informed consent.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".