TIL Therapy LN-145 Elicits 21.4% ORR in Previously Treated Metastatic NSCLC

The tumor-infiltrating lymphocyte (TIL) therapy LN-145 was found to induce an objective response rate (ORR) of 21.4% in patients with advanced or metastatic non–small cell lung cancer (NSCLC) who had progressed following systemic therapy, according to data from cohort 3B of the phase 2 IOV-COM-202 basket trial (NCT03645928).¹

Historically, ORRs of approximately 20% have been reported with immune checkpoint inhibitors as second-line therapy in patients who were naïve to these agents and who had progressed on first-line chemotherapy, according to Iovance Biotherapeutics, Inc., the drug developer.

Among those who responded to treatment, 1 patient achieved a complete response and 5 experienced partial responses. Notably, 85.7% of patients, including all responders, had previously received at least 2 lines of systemic therapy.² All patients had previously received a PD-1/PD-L1 therapy, and all responders had previously received chemotherapy.

At a median follow-up of 8.2 months, the median duration of response had not yet been reached (range, 1.2+ to 20.7+). The disease control rate was 64.3% (n = 18/28) following one-time treatment with the TIL therapy.

The company announced plans to present additional findings from cohort 3B at a medical conference in the second half of 2021.

“There remains a very significant unmet need to increase response rates and prolong survival in the second-line NSCLC treatment setting,” Friedrich Graf Finckenstein, MD, chief medical officer of Iovance, stated in a press release. “The initial data for LN-145 in this difficult-to-treat patient population is very promising.”

TIL therapy is derived from a patient’s own immune cells, or lymphocytes, that have come to the tumor site to eliminate the cancer.³ LN-145 is a novel immunotherapy developed from TILs. The therapy is a form of adoptive cell transfer in which TILs harvested from the patient’s tumor tissue are reinvigorated, expanded, and then infused into the patient.^4,5

The phase 2 basket trial is enrolling patients who have been diagnosed with histologically confirmed unresectable or metastatic melanoma, recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), recurrent or metastatic NSCLC, or relapsed or refractory NSCLC.

Beyond the examination of LN-145 monotherapy in patients with NSCLC who have received prior systemic therapy, including checkpoint inhibitors and TKIs, the trial is also looking at the following cohorts:

• LN-145 plus pembrolizumab (Keytruda) in patients with unresectable or metastatic HNSCC who have not previously received immunotherapy.
• LN-145 plus pembrolizumab in patients with recurrent or metastatic NSCLC who have not previously received immunotherapy
• LN-145 plus ipilimumab (Yervoy) and nivolumab (Opdivo) in patients with recurrent or metastatic NSCLC who have received 1 prior line of approved checkpoint inhibitor monotherapy as the only prior line of treatment.
• Lifileucel (formerly LN-144) plus pembrolizumab in patients with unresectable or metastatic melanoma who have not previously received immunotherapy. Patients whose tumors harbor BRAF mutations could have received a BRAF inhibitor.
• LN-145-S1 monotherapy in patients with unresectable or metastatic melanoma who have previously received at least 1 line of systemic therapy. Those with BRAF positivity could have received a prior BRAF inhibitor.
• Single-agent LN-144, manufactured using a third-generation process over the course of 16 days, in patients with unresectable or metastatic melanoma who have previously received at least 1 line of systemic therapy. Those with BRAF-mutant tumors may have received a BRAF inhibitor.

The overall objective of the research is to examine whether investigational TIL therapy is safe and effective in the treatment of several solid tumors and patient populations. Other goals include determining whether TIL therapy alone or plus pembrolizumab or ipilimumab/nivolumab is safe; whether TIL therapy monotherapy or plus pembrolizumab or ipilimumab/nivolumab can result in tumor reduction; and whether TIL monotherapy or plus pembrolizumab or ipilimumab/nivolumab can prolong life without worsening of disease, among others.

The safety profile of the approach was found to be consistent with the underlying disease and known toxicity profiles of non-myeloablative lymphodepletion and interleukin-2.

Additionally, the phase 2 IOV-LUN-202 trial (NCT04614103) is examining LN-145 in the second-line treatment of patients with metastatic NSCLC who have progressed on 1 previous immune checkpoint inhibitor and chemotherapy; the first patient has been dosed with treatment.

“We are excited to share our initial results for LN-145 in NSCLC, a new potential indication for Iovance TIL cell therapy, which show positive outcomes in patients with high unmet medical need,” Finckenstein added in the release. “We see a substantial opportunity to advance LN-145 in the post–immune checkpoint inhibitor setting for patients with lung cancer.”

References

1. Iovance Biotherapeutics announces clinical data for LN-145 in non-small cell lung cancer. News release. Iovance Biotherapeutics, Inc. June 29, 2021. Accessed July 7, 2021. https://bit.ly/3jRYj8h
2. IV-COM-202 cohort 3B: clinical data for LN-145 in patients with metastatic non-small cell lung cancer. Iovance Biotherapeutics, Inc. June 29, 2021. Accessed July 7, 2021. https://bit.ly/3Azv93Q
3. A phase 2, multicenter study of autologous tumor infiltrating lymphocytes in patients with melanoma, head and neck cancer, and non-small cell lung cancer (NSCLC). Iovance Biotherapeutics, Inc. Accessed July 7, 2021. https://bit.ly/3hlCiwV
4. Autologous LN-145 in patients with metastatic non‒small-cell lung cancer. ClinicalTrials.gov. Updated April 6, 2021. Accessed April 7, 2021. https://clinicaltrials.gov/ct2/show/NCT04614103
5. Massarelli E, Goldberg Z, Cacovean A, et al. Trial in progress: a phase 2, multicenter study of autologous tumor infiltrating lymphocytes (TIL, LN-145) cell therapy in patients with metastatic non-small cell lung cancer (IOV-LUN-202). Presented at: American Association for Cancer Research Annual Meeting 2021; April 10-15, 2021; virtual. Abstract CT246. https://www.abstractsonline.com/pp8/#!/9325/presentation/4856