497 Updated results from a phase 1 study of evalstotug (BA3071), an anti–CTLA-4 conditionally active biologic, with or without nivolumab, in advanced solid tumors

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Background Currently, toxicity limits dose density of CTLA-4 inhibitor + PD-1 inhibitor therapy in patients (pts) with advanced solid tumors.1–3 Evalstotug (BA3071) is a conditionally active biologic (CAB) anti–CTLA-4 monoclonal antibody that blocks the interaction of CTLA-4 with its ligands in the low-pH conditions of the tumor microenvironment.4 CABs are reversibly bound in the acidic tumor microenvironment, which reduces off-tumor immune-related adverse events, enhances host immunity, avoids tissue-mediated drug disposition, and improves pharmacokinetics. This multicenter, open-label, phase 1 study evaluated the safety and antitumor activity of evalstotug ± anti-PD-1 therapy in pts with advanced solid tumors. Methods Adult pts naive to anti–CTLA-4 therapy with advanced solid tumors and measurable disease per RECIST v1.1 received escalating doses of evalstotug every 3 weeks (Q3W) ± nivolumab. Treatment continued until disease progression or unacceptable toxicity. Safety was assessed using the NCI CTCAE v5, and efficacy was assessed using RECIST v1.1, with response assessment performed Q6W for 24 weeks, then Q12W until progression. Results Phase 1 enrollment has been completed. Twenty-one pts were treated with evalstotug (7–1000 mg) ± nivolumab (240 mg). Pts had received a median of 3 prior lines of therapy, and all pts had experienced failure of anti–PD-1 therapy. Three pts received evalstotug 1000 mg, and the observation period has been cleared for dose-limiting toxicity. The mean number of evalstotug doses overall and for 350 mg were 6.9 and 7.2, respectively. Most related treatment-emergent adverse events (TEAEs) were low grade. Four pts experienced grade 3 related TEAEs (atrial fibrillation, hypertension, diabetic ketoacidosis, and increased lipase with gastritis/diarrhea); no grade 4/5 related TEAEs were observed. Two patients discontinued treatment secondary to TEAEs (grade 3 atrial fibrillation [700 mg] and gastritis [350 mg]). Among 20 efficacy-evaluable patients, 6 experienced stable disease (disease control rate, 52%), and 3 of 8 patients who received evalstotug 350 mg responded (CR in cervical carcinoma [confirmed], PRs in gastroesophageal carcinoma [confirmed], and cutaneous melanoma [unconfirmed]). Three pts (2 with cutaneous melanoma and 1 with small cell lung cancer) remained without progression for >1 year. Conclusions Treatment with relatively high doses of evalstotug, with or without anti–PD-1 therapy, yielded confirmed responses with prolonged progression-free survival and a manageable safety profile, enabling continued treatment for extended intervals. The phase 2 study is ongoing to evaluate evalstotug ± anti-PD1 therapy ± chemotherapy. Acknowledgements This study was funded by BioAtla, Inc. Medical writing support was provided by Alec Jacobson, MD, from MedLogix Communications, a Citrus Health Group, Inc., company (Chicago, IL), and was funded by BioAtla, Inc. Trial Registration Clinical trial registry number: NCT05180799. References Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 2018;378(14):1277–1290. Antonia SJ, López-Martin JA, Bendell J, et al. Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol 2016;17(7):883–895. Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus ipilimumab in advanced non-small-cell lung cancer. N Engl J Med 2019;381(21):2020–2031. Chang HW, Frey G, Liu H, et al. Generating tumor-selective conditionally active biologic anti-CTLA4 antibodies via protein-associated chemical switches. Proc Natl Acad Sci USA 2021;118(9):e2020606118. Ethics Approval The study was performed in accordance with ethical principles that have their origins in the Declaration of Helsinki and are consistent with ICH/GCP.

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