American Association for Cancer Research Annual Meeting

American Association for Cancer Research Annual Meeting

Perspective from Kim Margolin, MD
Perspective from Philip D. Greenberg, MD
Perspective from Roman Groisberg, MD
Source:

Chesney JA, et al. Abstract CT008. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting); April 10-15, 2021.

Disclosures: Iovance Biotherapeutics sponsored the study. Chesney reports a consultant role with Amgen and research funding from Amgen, Bristol Myers Squibb and Iovance Biotherapeutics. Please see the abstract for all other researchers’ relevant financial disclosures.
April 15, 2021
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Tumor-infiltrating lymphocytes show ‘dramatic’ results in metastatic melanoma

Perspective from Kim Margolin, MD
Perspective from Philip D. Greenberg, MD
Perspective from Roman Groisberg, MD
Source:

Chesney JA, et al. Abstract CT008. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting); April 10-15, 2021.

Disclosures: Iovance Biotherapeutics sponsored the study. Chesney reports a consultant role with Amgen and research funding from Amgen, Bristol Myers Squibb and Iovance Biotherapeutics. Please see the abstract for all other researchers’ relevant financial disclosures.
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More than 80% of patients with heavily pretreated metastatic melanoma experienced tumor shrinkage after receiving the adoptive cell therapy lifileucel, according to results of a phase 2 study.

The study — presented during the virtual American Association for Cancer Research Annual Meeting — was the first to examine the efficacy of tumor-infiltrating lymphocytes (TILs) for unresectable or metastatic melanoma in the post-PD-1 inhibitor era, according to Jason A. Chesney, MD, PhD, director of James Graham Brown Cancer Center and associate vice president for health affairs at University of Louisville.

More than 80% of patients with heavily pretreated metastatic melanoma experienced tumor shrinkage after receiving the adoptive cell therapy lifileucel.
Data were derived from Chesney JA, et al. Abstract CT008. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting); April 10-15, 2021.

“There is very little to offer these patients that has been shown to improve outcomes,” Chesney told Healio, adding that, to his knowledge, there are no FDA-approved therapies for second-line use after treatment with immune checkpoint inhibitors.

Jason A. Chesney, MD, PhD
Jason A. Chesney

“As a practicing melanoma oncologist, these results are nothing short of dramatic and outstanding for this patient population,” he said. “It's transformative and not only gives patients hope, but the opportunity to live a long life.”

Lifileucel (LN-144, Iovance Biotherapeutics) is an adoptive cell therapy derived by isolating TILs from a resected portion of a patient’s tumor and multiplying them in a laboratory. The manufacturing process occurs at a centralized facility and takes 22 days, according to the researchers.

Chesney and colleagues presented results from cohort 2 of an open-label phase 2 study to determine the efficacy and safety of lifileucel among patients with unresectable metastatic melanoma. All participants experienced disease progression after receiving anti-PD-1 therapy, as well as BRAF/MEK inhibitors if they had BRAF V600-mutant disease.

The cohort included 66 patients (median age, 55 years; range, 20-79; 59% men) who received a mean 3.3 (range, 1-9) previous lines of therapy.

All patients previously received anti-PD-1/anti-PD-L1 therapy, and 80% previously received anti-CTLA-4 therapy.

The study regimen started with 1 week of nonmyeloablative lymphodepletion with 60 mg/kg IV cyclophosphamide and 25 mg/m2 fludarabine, followed by a single infusion of lifileucel. Patients then received up to six doses of interleukin (IL)-2 (600,000 IU/kg/dose) to promote TIL activity.

Efficacy as determined by the investigator-assessed objective response rate (ORR) served as the primary endpoint for the cohort 2 analysis. Secondary endpoints included safety and additional efficacy measurements.

Patients received a mean dose of 27.3 × 109 TIL cells.

Median follow-up was 28.1 months, with a data cutoff date of Dec. 14, 2020.

Results showed an objective response rate of 36.4%, with a complete response rate of 4.5%.

Forty-four percent of patients had stable disease after the regimen, for an overall disease control rate of 80.3%.

Median duration of response had not been reached (range, 2.2-35.2 months), which Chesney said indicates lifileucel induced “very durable responses.”

“The long game with many types of cancer is to turn it into a chronic illness. That means we don't need to eradicate the tumors; we need to just need to prevent the tumors from growing and spreading,” he told Healio. “This therapy clearly did that in our study population.”

Most toxicities were expected, related to lymphodepletion and hematologic in nature, Chesney said.

Grade 3 to grade 4 treatment-emergent adverse events occurred among 97% of patients and included thrombocytopenia (81.8%), anemia (56.1%), febrile neutropenia (54.5%), neutropenia (39.4%), hypophosphatemia (34.8%) and leukopenia (34.8%).

Two patients died during the study, one of intra-abdominal hemorrhage possibly related to TILs and one of acute respiratory failure deemed unrelated to TILs, according to the investigator’s evaluation.

“The TILs themselves are very safe,” Chesney told Healio.

However, he acknowledged “there is quite a bit of toxicity associated with high-dose IL-2,” which Chesney said has been well-established in previous studies because IL-2 is an FDA-approved treatment for stage IV melanoma.

“With that said, IL-2 can be given safely [to] patients who have adequate respiratory and cardiac function,” he said.

Although TILs remain investigational, they would represent perhaps the first option for late-stage melanoma that can improve patient outcomes if they receive commercial approval, Chesney said.

“This therapy is going to have a large, long-term impact on survival for our patients,” he said. “TILs are a very important treatment option for patients with stage IV melanoma after receiving therapy with immune checkpoint inhibitors. I believe the FDA is going to look favorably on these results."