Lifileucel Plus Pembrolizumab Yields Positive ORR in Advanced Cancers


Patients with melanoma, head and neck squamous cell carcinoma, and cervical cancer who had not previously received immunotherapy and were treated with lifileucel plus pembrolizumab experienced promising overall response rates compared favorably with historical data on pembrolizumab monotherapy.

Lifileucel (LN-144), an autologous adoptive cell therapy that utilizes tumor infiltrating lymphocytes (TILs), plus pembrolizumab (Keytruda) led to promising overall response rates (ORRs), including some complete responses (CRs), for patients with immune checkpoint inhibitor–naïve cervical cancer, melanoma, and head and neck cancer, according to results of 2 phase 2 trials that were presented at the 2021 Society for Immunotherapy of Cancer (SITC) Annual Meeting.1,2

In cohort 3 of the C-145-04 trial (NCT03108495), the ORR in 14 patients with persistent, recurrent, or metastatic cervical cancer was 57.1%, which included 1 CR to lifileucel plus pembrolizumab. In the IOV-COM-202 study (NCT-3645928), patients with advanced, recurrent, or metastatic melanoma who were treated in cohort 1A (n = 10) experienced an ORR of 60.0%, which included 3 CRs; those with advanced, recurrent, or metastatic head and neck squamous cell carcinoma (HNSCC; n = 18) treated in cohort 2A experienced and ORR of 38.9%, including 1 CR.

“We observed response rates that are approximately double compared to what was seen with single-agent pembrolizumab in early-line melanoma and head and neck cancers as well as second-line cervical cancer. We are eager to continue our investigation of TIL combinations in melanoma, head and neck, cervical and non-small cell lung cancer patients in need of treatment options that provide higher response rates, and deeper responses with more complete responses,” Friedrich Graf Finckenstein, MD, chief medical officer of Iovance, said in a press release.

To be eligible for the trial, patients had to have 1 or more resectable lesions for TIL manufacturing, 1 or more measurable lesions for response assessment, and an ECOG performance status of 0 or 1.

Patients received 1 dose of pembrolizumab at either 200 mg or 400 mg after tumor resection but before nonmyeloablative lymphodepletion (NMA-LD), then went on to receive NMA-LD with cyclophosphamide at 60 mg/kg daily for 2 doses and fludarabine for 25 mg/m2 daily for 5 doses. Patients then received a TIL infusion between 1 × 109 to 150 × 109 cells, with less than 6 doses of interleukin-2 every 8 to 12 hours for up to 3 to 24 hours after completion of TIL infusions. Patients continued pembrolizumab every 3 weeks at 200 mg or 6 weeks at 400 mg for less than 24 months.

Three patients (30%) in cohort 1A and 12 (66.7%) in cohort 2A received chemotherapy as prior systemic therapy. In cohort 2A, 9 patients (50%) received radiotherapy. In cohort 3, 9 patients (64.3%) received curative or therapeutic surgery, 7 (50.0%) received chemo-radiotherapy, and 3 (21.4%) received radiotherapy only.

At study entry, 13 patients (72.2%) in cohort 2A and 13 (92.9%) in cohort 3 had M1 metastasis; in cohort 1A, 2 (20.0%) had M1A and 7 (70.0%) had M1C metastases. In cohort 1A, 4 patients (40.0%) had PD-L1 negative disease, defined by a tumor proportion score (TPS) below 5%, compared with 3 (16.7%) in cohort 2A and 1 (7.1%) in cohort 3. PD-L1 positivity, defined at TPS 5% or greater. was observed in 5 (50.0%), 11 (61.1%), and 10 (71.4%) patients, respectively.

Patients with melanoma experienced 100% tumor reduction, compared with 87.5% of patients with HNSCC and 85.7% with cervical cancer. These responses were durable and continued to deepen over time.

At data cutoff, 4 out of 6 evaluable patients with melanoma (66.7%) had ongoing responses compared with 3 out of 6 (50.0%) with HNSCC, and 5 out of 7 (71.4%) with cervical cancer. The median study follow-up for those with melanoma was 11.5 months, 7.8 months for HNSCC, and 7.6 months for cervical cancer.

Grade 3 or 4 treatment-emergent adverse effects (TEAEs) in all cohorts (N = 42) occurred in 95.2% of patients. One patient in cohort 1 (10.0%) and 4 (22.2%) in cohort 2 experienced grade 5 TEAEs. The most common grade 3 or 4 TEAEs were thrombocytopenia in 22 patients (52.4%), anemia in 21 (50.0%), and neutropenia in 17 (40.5%).


1. Iovance Biotherapeutics announces clinical data for lifileucel in combination with pembrolizumab in advanced cancers at Society for Immunotherapy of Cancer (SITC) Annual Meeting. News Release. Iovance Biotherapeutics. November 13, 2021. Accessed November 16, 2021.

2. O’Malley D, Lee S, Psyrri A, et al. Phase 2 efficacy and safety of autologous tumor-infiltrating lymphocyte (TIL) cell therapy in combination with pembrolizumab in immune checkpoint inhibitor-naïve patients with advanced cancer. Presented at 2021 Society for Immunotherapy of Cancer Annual Meeting. November 10-14, 2021, Washington DC.

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