Sigvotatug vedotin (SV), an investigational integrin beta-6 (IB6)–directed antibody‒drug conjugate (ADC), and pembrolizumab combination therapy: Initial results from an ongoing phase 1 study (SGNB6A-001).
Kartik Sehgal, Jesus Corral Jaime, Steven Powell, Cesar A. Perez, Elisa Fontana, Ed Kingsley, Federico Longo Munoz, Sarina A. Piha‐Paul, Rachel E. Sanborn, Jonathan Hayman, Francesca Toffalorio, Tianhua Wang, Wyatt Chafin, Solange Peters
Abstract
3010 Background: IB6, a tumor-associated membrane protein, is overexpressed in many solid tumors, including non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC). SV, an IB6-directed ADC, demonstrated encouraging antitumor activity and manageable safety as a monotherapy in patients (pts) with advanced NSCLC in SGNB6A-001, an ongoing phase 1 study (Peters, ASCO 2024). Due to immunogenic cell death induction and innate immune system activation, SV activity may be enhanced when combined with pembrolizumab (P; SV+P). We report initial results of SV+P in pts with advanced solid tumors. Methods: SGNB6A-001 (NCT04389632) is an open-label, multicenter, dose-escalation and dose-expansion phase 1 study evaluating the safety, pharmacokinetics (PK), and antitumor activity of SV. Part C is evaluating safety of SV+P in pts with advanced solid tumors; part D is currently enrolling to evaluate SV+P in treatment-naive pts with locally advanced, unresectable, or metastatic NSCLC and HNSCC. Pts receive SV 1.8 mg/kg by adjusted ideal body weight IV Q2W and P 400 mg IV Q6W. Primary endpoint is safety; secondary endpoints include efficacy and PK. Results reported here are from parts C and D. Results: As of Nov 26, 2024, 31 pts received ≥1 dose of SV+P in parts C and D (19 NSCLC, 11 HNSCC, and 1 esophageal); median (95% CI) follow-up was 2.9 (1.6-5.0) months, and 26 pts remain on treatment. Median (range) age was 65 (34-80) years, 61% were male, and 52% had ECOG PS 0. Of pts with NSCLC, 12 (63%) had non-squamous tumors and 11 (58%) had tumors with PD-L1 TPS ≥1. All pts with HNSCC had tumors with PD-L1 CPS ≥1. Any-grade (Gr) and Gr ≥3 treatment-emergent adverse events (TEAEs) occurred in 87% and 35% of pts, respectively. Most common TEAEs are shown in the Table. Any-Gr and Gr ≥3 immune-mediated TEAEs occurred in 61% and 10% of pts, respectively. Pneumonitis/interstitial lung disease occurred in 3 pts (9.7%), with no Gr ≥3 events. Renal TEAEs led to discontinuation of both SV and P in 2 pts (6%); 3 other pts discontinued treatment (1 progressive disease, 2 consent withdrawal). There were no treatment-related deaths. In 7 efficacy-evaluable pts with TPS≥1 NSCLC, 1 confirmed (c) complete response (CR), 1 c partial response (PR), and 2 PRs pending confirmation were observed (ORR 57%; cORR 29%). In 8 efficacy-evaluable pts with 1L HNSCC, 2 cCR and 1 cPR were observed (cORR 37.5%). Conclusions: SV+P demonstrated manageable safety and encouraging preliminary efficacy. These data support the ongoing phase 3 Be6A-Lung-02 study (NCT06758401) comparing SV+P vs P as first-line treatment for pts with PD-L1 high (TPS≥50) advanced NSCLC. Clinical trial information: NCT04389632 . All Treated Pts (n=31) TEAEs Any Gr (>25%)n (%) Gr ≥3 n (%) Fatigue 13 (42) 1 (3) Decreased appetite 13 (42) 3 (10) Nausea 12 (39) 0 Alopecia 11 (35) 0 Asthenia 9 (29) 2 (6) Decreased weight 8 (26) 0 Dysgeusia 8 (26) 0