Amtagvi (lifileucel)

P1, N=20, Recruiting, Memorial Sloan Kettering Cancer Center | N=10 --> 20

P2, N=60, Recruiting, Iovance Biotherapeutics, Inc. | Not yet recruiting --> Recruiting

Despite these challenges, tumor-infiltrating lymphocyte (TIL) therapy, as exemplified by lifileucel, has demonstrated notable efficacy against BRAF V600-mutant melanoma. Additionally, early response biomarkers, such as COX-2 and MMP2, along with FDG-PET imaging, offer the potential to improve personalized immunotherapy by predicting patient responses and determining the optimal treatment duration. Future efforts should focus on reducing the T-cell harvesting periods and costs associated with TIL therapy to enhance efficiency and accessibility.

P1, N=40, Recruiting, Iovance Biotherapeutics, Inc.

The Gen 2 manufacturing process used for lifileucel successfully expanded functional TILs from RCC samples, enabling further study in a clinical trial. TIME features such as low CD8/FoxP3 ratio and high PD-1 expression within FoxP3 cells warrant study as potential biomarkers of successful TIL expansion.

P2, N=60, Not yet recruiting, Iovance Biotherapeutics, Inc.

P1, N=10, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2024 --> May 2025

P2, N=178, Recruiting, Iovance Biotherapeutics, Inc. | Trial completion date: Dec 2024 --> Aug 2029 | Trial primary completion date: Dec 2023 --> Aug 2029

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. 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.

P1, N=2, Active, not recruiting, Richard Wu | Recruiting --> Active, not recruiting | N=15 --> 2 | Trial completion date: Dec 2025 --> Dec 2024

P1, N=10, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

Based on the encouraging efficacy, tolerable safety profile, and advancements in a central manufacturing process, lifileucel is now the first US Food and Drug Administration (FDA)-approved TIL cell therapy product...These recommendations provide practical guidelines for optimal clinical management during administration of the TIL cell therapy regimen, and recognition of subsequent management of toxicities. These guidelines are focused on multidisciplinary teams of physicians, nurses, and stakeholders involved in the care of these patients.

P2, N=12, Recruiting, University of Kansas Medical Center | Trial primary completion date: Nov 2024 --> Nov 2025

Lifileucel, an FDA-approved tumor-infiltrating lymphocyte therapy, has demonstrated improved response rates in advanced-stage melanoma...While immunotherapy has significantly advanced melanoma treatment, its success varies, prompting research into new drugs and factors influencing outcomes. This review provides insights into current melanoma treatments and recent therapeutic advances.

P2, N=12, Recruiting, University of Kansas Medical Center | Not yet recruiting --> Recruiting

P2, N=12, Not yet recruiting, University of Kansas Medical Center

P2, N=178, Active, not recruiting, Iovance Biotherapeutics, Inc. | Trial primary completion date: Jul 2021 --> Jan 2025

P1, N=10, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

Of 153 pts who received lifileucel, 109 (71%) were primary resistant (SITC definition) and 83 (54%) were primary refractory (study definition). In primary resistant pts, ORR with lifileucel was 33% (95% CI: 24%, 43%) and median DOR was not reached (NR; 95% CI: 12.5 mo, NR). In primary refractory pts, ORR was 31% (95% CI: 22%, 42%) and median DOR was NR (95% CI: 15.1 mo, NR).

P1, N=10, Recruiting, Memorial Sloan Kettering Cancer Center

P1, N=15, Recruiting, Richard Wu | Phase classification: P1/2 --> P1

Background Aldesleukin (IL-2), at high doses in repeat cycles, is approved as monotherapy for patients (pts) with metastatic melanoma...Methods Pts with advanced melanoma received cyclophosphamide and fludarabine (NMA-LD, Day –7 to –1), a single lifileucel infusion (Day 0), and ≤6 IL-2 doses (600,000 IU/kg) every 8–12 h (Day 0–4)...Pts with disease refractory to prior IL-2 monotherapy derived benefit from lifileucel. Presence of G3/4 lymphopenia in all pts at time of IL-2 administration argues against a direct antineoplastic effect of abbreviated IL-2 dosing as part of the lifileucel regimen.

P=N/A, Available, Iovance Biotherapeutics, Inc.

Available cases from C1A (ICI-naïve pts receiving lifileucel + pembrolizumab [pembro]) were matched to controls from C2 (pts receiving lifileucel alone after progression on anti?PD-1/PD-L1 therapy); 3 controls per case were matched at least for BRAF status and disease stage at study entry, and if possible, for anatomic site of tumor harvest. Our preliminary data indicate that the efficacy (ORR) of lifileucel may be independent of TMB, regardless of treatment setting, consistent with its proposed immune checkpoint pathway-independent mechanism of action. The percentage of patients with high TMB tended to be lower in tumors with prior ICI exposure than in those that were ICI-naïve.

P1/2, N=15, Recruiting, Richard Wu | Not yet recruiting --> Recruiting

Background: Lifileucel TIL cell therapy has demonstrated safety and activity in treating patients with advanced melanoma Sarnaik AA, et al... Time to ship fresh tumors from Australia ≥3 days was substantially longer than our experience with tumors shipped within the US <1–2 days, data on file, and logistical challenges may limit the utility of this treatment using fresh tumors . Tumors that were frozen locally in Australia prior to shipment consistently produced sufficient dose for TIL treatment 4/4 samples; TIL manufacturing using fresh tumors was less reliable 3/4 samples. Additional tumor samples will be analyzed to continue optimizing the TIL manufacturing process using samples from Australia.

P1/2, N=15, Not yet recruiting, Richard Wu

Therapy consisted of nonmyeloablative lymphodepletion (cyclophosphamide / fludarabine), a single lifileucel infusion, followed by up to 6 doses of IL-2. post-therapy. Median DOR was still not reached at median follow-up of 28 month of study follow up, and 11 patients (17%) had further SOD reduction since previous data cut of Apr2020. Iovance is investigating lifileucel in earlier disease settings, in combination with ICI, and in other metastatic solid malignancies.

P2, N=178, Active, not recruiting, Iovance Biotherapeutics, Inc. | Trial primary completion date: Jul 2020 --> Jul 2021

P2, N=135, Recruiting, Iovance Biotherapeutics, Inc. | N=75 --> 135

Lifileucel treatment results in a 36.4% ORR and mDOR was not reached at 17.0 months of median study follow up in a heavily pretreated metastatic melanoma patients with high baseline disease burden who progressed on multiple prior therapies, including anti-PD1 and BRAF/MEK inhibitors, if BRAFv600 mutant. Research Funding: Iovance Biotherapeutics, Inc.

P2, N=178, Active, not recruiting, Iovance Biotherapeutics, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Mar 2020 --> Jul 2020