Abstract Background: CVL006 is a novel bispecific antibody designed for synergic antitumor activity by simultaneously blocking two mechanistically distinct pathways VEGF/VEGFR signaling and the PD-L1/PD-1 axis. In this phase I/II Clinical Study of CVL006 combo with pemetrexed and carboplatin, or SKB264, or DS8201, or Enfortumab Vedotin, Safety, pharmacokinetics (PK) and preliminary efficacy will be assessed in adult subjects with advanced solid tumors, and, thus, the recommended phase II dose (RP2D) will be established (NCT07157956). Methods: This is a multicenter, open-label, phase I/II dose-escalation and dose-optimization clinical study. Phase I dose-escalation involves dose escalation of CVL006 in combination therapy across four cohorts: Arm 1. 1, CVL006 combined with Pemetrexed plus Carboplatin; Arm 1. 2, CVL006 combined with SKB264; Arm 1. 3, CVL006 combined with DS-8201a; and Arm 1. 4, CVL006 combined with Enfortumab Vedotin. Pemetrexed plus Carboplatin, SKB264, DS-8201a, and Enfortumab Vedotin are administered at fixed doses, and all cohorts utilize a "3+3" design for dose escalation. Phase II Dose-Optimization Study with 9 Arms: To further evaluate anti-tumor activity of CVL006 in combination with Pemetrexed plus Carboplatin, SKB264, DS-8201a, or Enfortumab Vedotin. Patients will receive continuous treatment until disease progression (assessments every 8 weeks), voluntary withdrawal of consent, intolerable toxicity, or investigator-determined withdrawal from the study. Results: As of the data cutoff date of December 9, 2025, 6 subjects with advanced tumors were enrolled in phase I received CVL006 at 10 mg/kg, 3 subjects in Arm 1. 1, 3 subjects in Arm 1. 2. Phase I results show that CVL006 combo with pemetrexed and carboplatin, or SKB264 is well-tolerate, MTD has not reached. In Arm 1. 1, The incidence of CVL006 treatment-related AEs (TRAEs) was 66. 7% (2/3), all Grade 1, no DLT and no ≥ Grade 2 AEs; In Arm 1. 2, The incidence of CVL006 treatment-related AEs (TRAEs) was 100% (3/3), most were Grade 1, no DLT and no ≥ Grade 3 AEs. All these AEs were recovered after symptomatic treatment. In the 10 mg/kg dose group, CVL006 showed no incidence of ADA positivity. 2 subjects had at least one efficacy assessment in Arm 1. 2 (N=3), 1 partial response (PR), 1 stable disease (SD) (tumor shrinkage of 28. 57%), with an ORR of 33% and DCR of 66. 7%. Conclusion: CVL006 combo with pemetrexed and carboplatin, or SKB264 appeared to be well tolerated and had encouraging preliminary efficacy in patients with advanced solid tumors, warranting further investigation. Citation Format: Steve Shen, Li Zhang, Wenfeng Fang. Phase I/II clinical trial of CVL006 combination therapy in advanced solid tumors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr CT095.
Shen et al. (Fri,) studied this question.