FDA Updates Highlighting the Latest Cancer Treatments

Accelerated Approval of Loncastuximab GEJ adenocarcinoma in combination with and chemo- Tesirine-Lpyl for Large B-Cell therapy is 200 mg every 3 weeks or 400 mg every 6 weeks. The FDA granted accelerated approval to loncastuximab tesirine-lpyl, a CD19-directed antibody and alkylating agent conjugate, for adult Orphan Drug Designation for BOLD-100 as patients with relapsed or refractory large B-cell lymphoma after two Treatment of Gastric Cancer or more lines of systemic therapy, including diffuse large B-cell lym- BOLD-100 received orphan drug designation in the treatment of gas- phoma (DLBCL) not otherwise specified, DLBCL arising from low- tric cancer. BOLD-100 is a first-in-class ruthenium-based small mol- grade lymphoma, and high-grade B-cell lymphoma. ecule therapeutic that: 1) alters the unfolded protein response through Approval was based on LOTIS-2 (NCT03589469), an open-label, selective GRP78 inhibition; and 2) induces reactive oxygen species single-arm trial in 145 adult patients with relapsed or refractory that causes DNA damage and cell cycle arrest. Collectively, these ef- DLBCL or high-grade B-cell lymphoma after at least two prior sys- fects result in cell death in both sensitive and resistant cancers, giving temic regimens. Patients received loncastuximab tesirine-lpyl 0.15 mg/ BOLD-100 the potential to significantly improve outcomes in a wide kg every 3 weeks for 2 cycles, then 0.075 mg/kg every 3 weeks for sub- range of both solid and liquid tumors in combination with other anti- sequent cycles. Patients received treatment until progressive disease or cancer therapies ranging from traditional to targeted unacceptable toxicity. therapies. The main efficacy outcome measure was overall response rate Patients are actively being enrolled in the Phase Ib trial of BOLD- (ORR), as assessed by an independent review committee using Lugano 100 in combination with FOLFOX (5-fluorouracil, leucovorin, oxali- 2014 criteria. The ORR was 48.3 percent (95% CI: 39.9, 56.7) with a platin) for the treatment of patients with advanced gastrointestinal complete response rate of 24.1 percent (95% CI: 17.4, 31.9). After a cancers at six sites in Canada: Cross Cancer Institute (Edmonton, median follow-up of 7.3 months, median response duration was 10.3 Alberta); Princess Margaret Cancer Centre (Toronto); Ottawa General months (95% CI: 6.9, NE). Of the 70 patients who achieved objective Hospital (Ottawa, Ontario); Juravinski Cancer Centre (Hamilton, responses, 36 percent were censored for response duration prior to 3 Ontario); Jewish General Hospital (Montreal); and Royal Victoria months. Hospital (Montreal). This adaptive design trial is expected to transi- Most common (≥20%) adverse reactions in patients receiving tion into a Phase II trial later this year, with additional clinical sites to loncastuximab tesirine-lpyl, including laboratory abnormalities, are be added in both the U.S. and South Korea. thrombocytopenia, increased gamma-glutamyltransferase, neutrope- nia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoal- Orphan Drug Designation for ITIL-168 in buminemia, rash, edema, nausea, and musculoskeletal pain. The prescribing information provides warnings and precautions The FDA granted an orphan drug designation to ITIL-168 TIL for adverse reactions, including edema and effusions, myelosuppres- therapy for the treatment of melanoma stages IIB-IV. ITIL-168 sion, infections, and cutaneous reactions. is an ­investigational, autologous cell therapy made from tumor-­ The recommended loncastuximab tesirine-lpyl dosage is 0.15 mg/ infiltrating lymphocytes (TILs). kg every 3 weeks for 2 cycles, then 0.075 mg/kg every 3 weeks for sub- The treatment is manufactured with a scalable manufacturing pro- sequent cycles, by intravenous infusion over 30 minutes on day 1 of cess which has been designed to capture and preserve the maximum each cycle (every 3 weeks). Patients should be premedicated with dexa- diversity of each patient’s TILs. The manufacturing process also offers methasone 4 mg orally or intravenously twice daily for 3 days begin- significant scheduling flexibility for patients and physicians at the time ning the day before loncastuximab tesirine-lpyl. of both tumor resection and TIL treatment. Researchers plan to investigate ITIL-168 in a global Phase II trial in Accelerated Approval of for advanced melanoma in 2021 and additional solid tumor indications HER2-Positive Gastric Cancer in Phase I clinical trials beginning in 2022. The FDA granted accelerated approval to pembrolizumab in combina- tion with trastuzumab, fluoropyrimidine- and platinum-containing FDA Breakthrough Device Designation for for the first-line treatment of patients with locally ad- Technology to Treat Prostate Cancer vanced unresectable or metastatic HER2-positive gastric or gastro- Breakthrough Device Designation was awarded for a male “lumpec- esophageal junction (GEJ) adenocarcinoma. tomy” product in development designed to treat prostate cancer in- Approval was based on the prespecified interim analysis of the first office while preserving quality of life. 264 patients of the ongoing KEYNOTE-811 (NCT03615326) trial, a The Avenda Health Focal Therapy System, which is designed to multicenter, randomized, double‑blind, placebo‑controlled trial in pa- spare healthy tissue and minimize side effects, uses patient-specific tients with HER2‑positive advanced gastric or GEJ adenocarcinoma information and artificial intelligence to deliver a precise and person- who had not previously received systemic therapy for metastatic dis- alized treatment, targeting only the tumor. This treatment can be per- ease. Patients were randomized (1:1) to receive pembrolizumab 200 formed in a physician’s office with just local anesthesia, minimizing mg or placebo every 3 weeks, in combination with trastuzumab and the patient’s downtime and potentially reducing cost to the health care either fluorouracil plus cisplatin or capecitabine plus oxaliplatin. system. The main efficacy measure for this analysis was overall response rate (ORR) assessed by blinded independent review committee. The -Ejfv in Locally ORR was 74 percent (95% CI 66, 82) in the pembrolizumab arm and Advanced or Metastatic Urothelial Cancer 52 percent (95% CI 43, 61) in the placebo arm (one-sided p< 0.0001, The FDA filed two supplemental Biologics License Application statistically significant). The median duration of response was 10.6 (sBLA) submissions for enfortumab vedotin-ejfv for review as part months (range 1.1+, 16.5+) for patients treated with pembrolizumab of the Real-Time Oncology Review pilot program. The applications and 9.5 months (range 1.4+, 15.4+) for those in the placebo arm. were granted Priority Review, with a target action date of August The adverse reaction profile observed in patients receiving pem- 17, 2021. The review of both applications will also be conducted brolizumab in the study KEYNOTE-811 is consistent with the known under Project Orbis, an initiative of the FDA Oncology Center of pembrolizumab safety profile. Excellence. The recommended pembrolizumab dose for adult patients with The first sBLA is based on the Phase III EV-301 trial and seeks to locally advanced unresectable or metastatic HER2-positive gastric or convert the enfortumab vedotin-ejfv accelerated approval to regular

36 Oncology Times June 5, 2021 ­approval. The EV-301 trial (NCT03474107) is a global, multicenter, ease control rate, progression-free survival, overall survival, safety, and open-label, randomized trial designed to evaluate enfortumab vedo- tolerability. tin versus physician’s choice of chemotherapy (docetaxel, paclitaxel, Health authorities in Australia and Canada will evaluate data from or vinflunine) in approximately 600 patients with locally advanced or EV-301 and EV-201 for initial registrations under Project Orbis. In metastatic urothelial cancer who were previously treated with a PD-1/ March, the companies announced regulatory submissions in Japan L1 inhibitor and a platinum-based therapy. The primary endpoint is and the European Union. overall survival and secondary endpoints include progression-free In 2019, enfortumab vedotin-ejfv received accelerated approval in survival, overall response rate, duration of response, and disease con- the U.S. for the treatment of adult patients with locally advanced or trol rate, as well as assessment of safety/tolerability and quality-of-life metastatic urothelial cancer who have previously received a PD-1/L1 parameters. inhibitor and a platinum-containing chemotherapy before or after The second sBLA, based on the pivotal trial EV-201 cohort 2, re- surgery or in a locally advanced or metastatic urothelial cancer set- quests an expansion of the current indication to include patients ting. Enfortumab vedotin-ejfv is currently only approved for use in with locally advanced or metastatic urothelial cancer who have been the U.S. OT previously treated with a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and are ineligible for cisplatin. Results from EV-301 were published in the New England Have Stories Delivered Journal of Medicine. Results from EV-301 and EV-201 cohort 2 were presented at the 2021 ASCO Genitourinary Cancers Symposium. The EV-201 trial (NCT03219333) is a single-arm, dual-cohort, Directly to You pivotal Phase II of enfortumab vedotin for patients Sign up for our free oncology-times.com with locally advanced or metastatic urothelial cancer who have  e-newsletter and receive email / been previously treated with a PD-1 or PD-L1 inhibitor, includ- notifications when each issue ing those who have also been treated with a platinum-containing becomes available and when other new content is chemotherapy(cohort 1) and those who have not received a plati- posted online. New to Oncology Times? Visit the num-containing chemotherapy in this setting and who are ineligible publication’s website at www.oncology-times.com for cisplatin (cohort 2). where you can get free access to archived issues, The trial enrolled 128 patients in cohort 1 and 91 patients in cohort subscribe to the print magazine, and create your own 2 at multiple centers internationally. The primary endpoint is con- personal online article collections. firmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, dis-

Get the latest cancer related news from the Food and Drug Administration

Access the FDA Actions & Updates Blog online at Oncology-times.com

7-Q887

oncology-times.com Oncology Times 37