FDA Grants Orphan Drug Status to ITIL-168 for Melanoma

The FDA has granted an Orphan Drug designation to the investigational tumor-infiltrating lymphocyte (TIL) therapy ITIL-168 for the treatment of patients with stage IIB to IV melanoma.¹

“The Orphan Drug Designation incentivizes biotech companies to develop new therapies that are important for patients. We are pleased to advance development of ITIL-168 for the treatment of melanoma stages IIB to IV with this designation,” said Bronson Crouch, chief executive officer of Instil Bio, Inc.

ITIL-168 is described as an investigational, autologous cell therapy comprised of TILs. Through its manufacturing process, the treatment is designed to capture and preserve the maximum diversity of each individual’s patient’s TILs, the company stated.

Furthermore, the manufacturing process of ITIL-168 allows for scheduling flexibility for both physicians and patients at the time of tumor resection as well as TIL therapy.

In 2021, ITIL-168 is expected to be investigated in an international, phase 2 trial in advanced melanoma. The treatment will be studied in additional solid tumor indications in phase 1 studies in the beginning of 2022.

TIL therapy has been an active area of investigation in melanoma. For example, in the phase 2, international, single-arm, C-144-01 trial (NCT02360579), the TIL treatment lifleucel (LN-144) is being explored in patients with stage IIIC or IV unresectable or metastatic melanoma who have progressed on at least 1 prior systemic therapy, including a PD-1 inhibitor and BRAF or BRAF/MEK inhibition, the latter of which for patients who are BRAF mutant.²

The C-144-01 study has 4 cohorts: patients who received “first-generation” lifileucel therapy that had not been cryopreserved (cohort 1), and those who were treated with “second-generation” cryopreserved lifileucel therapy (cohorts 2-4).² All 3 primary cohorts are fully enrolled, with cohort 3 serving as an experimental retreatment subgroup for patients in cohort 2 who experience progression following TIL therapy. Cohort 4 has been adapted so that all patients with BRAF mutation–positive disease were previously treated with a BRAF or BRAF/MEK inhibitor.

After the manufacturing process is completed, the expanded TILs are cryopreserved and shipped back to the site where the patient is undergoing. Lifileucel is then administered intravenously, and then patients immediately receive up to 6 doses of interleukin 2 (IL-2).

Findings from cohort 2 were presented in 2020.³ Here, 66 patients with high baseline tumor burden who had received a mean of 3.3 prior therapies received lifileucel. At a median study follow-up of 18.7 months, the objective response rate was 36.4%; the partial response (PR) rate was 33.3% and the complete response (CR) rate was 3.0%.

Additional data showed that the stable disease rate was 43.9% and the disease control rate was 80.3%. A total 13.9% of patients experienced progressive disease. The median duration of response was not reached (range, 2.2 to 26.9+ months).

Updated results of a median 28.1 months of follow-up of the phase 2 study were presented during the virtual 2021 AACR Annual Meeting.⁴ The longer data showed that the ORR was 36.4% and the median DOR was still not reached (range 2.2 to 35.2+ months). The ORR comprised a 4.5% CR rate and a 31.8% PR rate.

Regarding safety, lifileucel was found to be consistent with the disease setting, lymphodepletion, and the IL-2 regimens that were utilized used, and investigators noted that the frequency of adverse events decreased over time.

References

1. Instil Bio receives Orphan Drug Designation for ITIL-168 in melanoma. News release. Instil Bio, Inc. April 27, 2021. Accessed April 27, 2021. https://bit.ly/3tYK2c6
2. Study of lifileucel (LN-144), autologous tumor infiltrating lymphocytes, in the treatment of patients with metastatic melanoma (LN-144). ClinicalTrials.gov. Updated January 21, 2020. Accessed April 27, 2021. https://clinicaltrials.gov/ct2/show/NCT02360579
3. Sarnaik A, Khushalani NI, Chesney JA. Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies. J Clin Oncol. 2020;38(suppl 15):10006. doi:10.1200/JCO.2020.38.15_suppl.10006
4. Chesney JA, Larkin JMG, Kirkwood JM, et al. Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced (unresectable or metastatic) melanoma: sustained duration of response at 28 month follow up. Presented at: 2021 AACR Annual Meeting; April 10-15, 2021; virtual. CT008.