American Association for Cancer Research Annual Meeting

American Association for Cancer Research Annual Meeting

Perspective from Lisa Butterfield, PhD
Perspective from Jason Bock, PhD
Perspective from Kim Margolin, MD
Source:

Hawkins RE, et al. Abstract LB-150. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting); April 10-15, 2021.

Disclosures: Instil Bio sponsored the study. Hawkins and Roberts report employment by and equity ownership in Instil Bio. Please see the abstract for all other researchers’ relevant financial disclosures.
April 23, 2021
3 min read
Save

Tumor-infiltrating lymphocytes show ‘provocative’ response rates in advanced melanoma

Perspective from Lisa Butterfield, PhD
Perspective from Jason Bock, PhD
Perspective from Kim Margolin, MD
Source:

Hawkins RE, et al. Abstract LB-150. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting); April 10-15, 2021.

Disclosures: Instil Bio sponsored the study. Hawkins and Roberts report employment by and equity ownership in Instil Bio. Please see the abstract for all other researchers’ relevant financial disclosures.
You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.com.

More than half of patients with heavily pretreated melanoma responded to therapy with unselected tumor-infiltrating lymphocytes, according to results of a retrospective study.

Researchers derived the data, presented during the virtual American Association for Cancer Research Annual Meeting, from a single-center evaluation of tumor-infiltrating lymphocytes (TILs) administered to patients with late-stage melanoma via a compassionate use protocol.

More than half of patients with heavily pretreated melanoma responded to therapy with unselected tumor-infiltrating lymphocytes.
Data derived from Hawkins RE, et al. Abstract LB-150. Presented at: American Association for Cancer Research Annual Meeting (virtual meeting); April 10-15, 2021.

The study started more than a decade ago and built upon previous TIL research conducted by the NCI, according to Robert E. Hawkins, MD, PhD, chief strategy advisor for Instil Bio and honorary professor of medical oncology at University of Manchester.

Hawkins and colleagues sought to determine the feasibility of providing TIL therapy outside the NCI — at an academic medical center —and to patients with disease progression after all other standard therapies.

Robert E. Hawkins, MD, PhD
Robert E. Hawkins

“We have a slightly different manufacturing process than what the NCI uses,” he told Healio. “There were distinct regulations around manufacturing in Europe that required some changes from the NCI process.”

The Instil Bio process used autologous unselected TILs from digested tumor tissue that were produced under a manufacturing specials license issued by the U.K.’s Medicines and Healthcare products Regulatory Agency. The shorter manufacturing process, compared with other methods, enables the final TIL product to contain the widest spectrum of T-cell receptor reactivity possible, according to Hawkins.

The study included 21 patients (median age, 45 years; range, 16-68; 71% men), all of whom had stage IV relapsed or refractory advanced cutaneous melanoma.

Patients received a median three (range, 1-9) lines of previous therapy, and 91% had received an immune checkpoint inhibitor. Fifty-two percent of patients had BRAF-mutant disease, and all of them previously received BRAF and/or MEK inhibitors.

All patients initially were hospitalized for study treatment, which consisted of nonmyeloablative lymphodepletion with 60 mg/kg cyclophosphamide daily for 2 days and 25 mg/m2 fludarabine daily for 5 days followed by TIL infusion and high-dose interleukin-2 (600,000 IU/kg to 720,000 IU/kg) to promote TIL activity.

Patients received a median 32 × 109 (range, 8 × 109 to 63 × 109) TIL cells and a median eight (range, 4-11) doses of IL-2.

Researchers evaluated efficacy among 15 patients based on locally assessed CT/MRI per RECIST version 1.1 and among the remaining six patients based on non-RECIST imaging, such as PET, and clinical monitoring.

Median follow-up was 52.2 months, with a data cutoff date of Dec. 31, 2019.

Safety results showed all patients experienced at least one treatment-related adverse event, including thrombocytopenia (62%), pyrexia (57%) and rigors (43%). Researchers observed no treatment-related deaths.

Zachary J. Roberts, MD, PhD
Zachary J. Roberts

"All the toxicity we have seen in our study is consistent with what has been reported in other clinical trials of TILs in that toxicity is related to preconditioning chemotherapy and the administration of IL-2,” Zachary J. Roberts, MD, PhD, chief medical officer for Instil Bio, told Healio. “These toxicities tended to be self-limited and managed supportively. Some patients spent a few days in the hospital and then were discharged with no further toxicities observed.”

The overall response rate among 15 imaging-evaluable patients was 53%, with a 67% ORR for the entire study population. Two patients (13%) in the imaging-evaluable group had a complete response to therapy, compared with four (19%) in the entire study population.

Three imaging-evaluable patients (20%) had stable disease, for an overall disease control rate of 73%.

Median OS was 21.3 months (95% CI, 6.8 to not estimable) for the entire study population and not yet reached for patients who had a complete or partial response to therapy.

Five patients (24%) had ongoing responses to therapy more than 30 months after TIL infusion, and all patients who had a complete response to therapy were alive and disease-free as of the data cutoff date.

Although it is too early to declare their TIL process more effective than other approaches, which would require further comparison studies, “our response rates are provocative,” Roberts told Healio.

“Part of what makes our process exciting and relevant in this era of added attention on TILs is its flexibility,” he said. “It's a measurably different process that allows us the potential to rapidly scale our clinical trial development program. If we end up achieving FDA approval for this therapy, our approach will end up significantly improving logistics in the commercial setting.”

Hawkins said the response rates are clinically meaningful compared with a 2019 systematic review and meta-analysis that showed a 41% ORR for TILs in this patient population.

“There was a very high response rate, with some complete remissions,” he said, adding that the treatment appears to be durable among those who had a complete response, whereas many other patients achieved stable disease with reduced tumor burden.

“The therapy improves patients' quality of life and can be quite durable,” Hawkins said. “Overall, it is very beneficial to patients."

Reference:

Danfi U, et al. Ann Oncol. 2019;doi:10.1093/annonc/mdz398.