XB002 Demonstrates Promising Early Safety Findings in Advanced Solid Tumors

Treatment with next-generation tissue factor–targeting antibody-drug conjugate XB002 resulted in promising early safety data in patients with advanced solid tumors for whom standard therapies were unavailable, ineffective, or intolerable, according to a press release on an initial readout of the phase 1 JEWEL-101 trial (NCT04925284).

Although the recommended dose and maximum tolerated dose had not been reached, investigators reported that there were no dose-limiting toxicities. A total of 42% of the total population (n = 19) experienced grade 3 treatment-emergent adverse effects (TEAEs) with no reports of grade 4 or 5 TEAEs. Treatment-related AEs occurred in 63% of patients, all of which were grade 2 and lower with the exception of 1 event of grade 3 hypertension; all AEs were improved or resolved prior to the following dose of XB002.

Serious AEs occurred in 16% of patients and were considered to not be related to treatment; this included grade 3 COVID-19 pneumonia and diarrhea occurring in 2 patients each, as well as grade 2 bacteremia. Despite 42% of patients being treated with anticoagulants, no bleeding events occurred.

“Following promising preclinical data, it is encouraging to see that XB002 was well-tolerated across multiple dose levels with a pharmacokinetic analysis supporting the ability of XB002 to remain stable after infusion and reach its target before releasing its cytotoxic payload,” Susanna Ulahannan, MD, MMed, an assistant professor of Medicine in the Section of Hematology/Oncology, University of Oklahoma College of Medicine and associate director of Oklahoma TSET Phase 1 Program, Oklahoma University (OU) Health Stephenson Cancer Center, OU Health Sciences Center, said in the press release. “As the dose-escalation phase progresses, and we initiate enrollment into tumor-specific cohorts, I look forward to learning more about how XB002 may benefit [patients] with advanced solid tumors, in particular in tumor types with a high unmet need.”

Several escalating dose levels of XB002 were included in the study, including 0.16 mg/kg (n = 3), 0.5 mg/kg (n = 3), 1.0 mg/kg (n = 6), 1.5 mg/kg (n = 3), and 2.0 mg/kg (n = 4). Frequent disease types included pancreatic, colorectal, cervical cancer, and prostate cancer. Patients had a median age of 63 years, and most had an ECOG performance status of 1 (63%) and 3 prior lines of therapy (79%).

Stable disease was achieved in 1 patient with metastatic castration-resistant prostate cancer, 1 with appendiceal adenocarcinoma, and 1 with pancreatic adenocarcinoma who had treatment durations of 42 weeks, 10 weeks, and 7 weeks, respectively, and they all remain on treatment. Another patient with uterine carcinosarcoma discontinued XB002 at 15 weeks after achieving stable disease as a best response.

In terms of other adverse effects, investigators reported the occurrence of ocular TEAEs in 42% of patients, including noninfective conjunctivitis (26%) and dry eye (16%). Ocular events appeared to occur more in the 2 mg/kg dose level (75%) vs other dose levels (33%). Investigators did not observe corneal toxicity, and all ocular events were reversible with supportive care. This included lubricating, vasoconstrictive, corticosteroid, and/or antibiotic eyedrops.

Investigators stated that XB002 will be assessed both alone and in combination with nivolumab (Opdivo) as part of an upcoming cohort expansion portion of the study

“We are pleased to present the first clinical profile of XB002 at ENA [Emergency Nurses Association] 2022, representing an important milestone for our first biologic in clinical development,” Vicki L. Goodman, MD, executive vice president of Product Development and Medical Affairs, and chief medical officer at Exelixis, concluded. “We are eager to proceed to the expansion cohort stage of JEWEL-101 once the recommended dose is determined, as we aim to further understand the activity of this molecule as a potential new treatment for people who have difficult-to-treat tumors with limited treatment options.”

Reference

Exelixis announces promising initial dose-escalation results from the first-in-human phase 1 JEWEL-101 trial evaluating XB002 in patients with advanced solid tumors at ENA 2022. News release. Excelixis. October 26, 2022. Accessed October 27, 2022. http://bit.ly/3TNY7pR