Phase Ib Study of Immunocytokine Simlukafusp Alfa (FAP-IL2v) Combined with Pembrolizumab for Treatment of Advanced and/or Metastatic Melanoma
Bibliographic record
Abstract
PURPOSE: This study explored the combination of fibroblast activation protein (FAP) IL2 variant (FAP-IL2v), a novel immune-cytokine, with pembrolizumab in patients with advanced and/or metastatic melanoma. PATIENTS AND METHODS: This open-label, multicenter, phase Ib clinical study (NCT03875079) evaluated the safety, tolerability, pharmacodynamics, pharmacokinetics, and antitumor activity of FAP-IL2v (simlukafusp alfa, RO6874281) in combination with pembrolizumab. Patients with advanced and/or metastatic melanoma were either checkpoint inhibitor (CPI)-naïve or CPI-experienced. Patients received 10 mg FAP-IL2v either continuously once every 3 weeks (Q3W) or in an induction/maintenance setting consisting of a 3-week induction phase with weekly (QW) dosing followed by continuous Q3W dosing. Pembrolizumab was dosed Q3W at 200 mg. RESULTS: Eighty-three patients were treated: 16 patients in two safety run-in cohorts and 67 patients in two extension cohorts; 75 (90.4%) patients were CPI-experienced. The pharmacokinetics of FAP-IL2v in combination with pembrolizumab was similar to that after administration as monotherapy. Consistent with the proposed mode of action, FAP-IL2v preferentially expanded NK and CD8 T cells. The most common FAP-IL2v-related grade 3/4 adverse events were lymphopenia (23%), elevated γ-glutamyltransferase (8%), elevated alanine aminotransferase (6%), and infusion-related reaction (6%). A response was observed in 5 of 75 (6.7%) CPI-experienced patients (all partial responses) and 2 of 8 CPI-naïve patients (one complete response and one partial response). The median progression-free survival was 3.1 months. CONCLUSIONS: The safety profile of FAP-IL2v in combination with pembrolizumab was manageable and consistent with the known safety profile. However, further exploration of FAP-IL2v and pembrolizumab was precluded in patients with melanoma with prior CPI due to the lack of clinical activity. SIGNIFICANCE: In this phase Ib study, the combination of FAP-IL2v, an immune-cytokine developed to overcome the limitations of wild-type IL2, with the CPI pembrolizumab did not show meaningful antitumor activity in patients who had progressed on prior CPI therapy, suggesting that FAP-IL2v alone cannot overcome CPI resistance or unresponsiveness.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".