P‑Sam for Adenoid Cystic Carcinoma – Phase 2 Clinical Trial
Puxitatug Samrotecan (P‑Sam) is a novel antibody‑drug conjugate that has shown a manageable safety profile and preliminary evidence of clinical benefit in early trials for adenoid cystic carcinoma.
Recurrent/metastatic adenoid cystic carcinoma (ACC) is a rare, incurable disease. MYB is a putative oncogenic driver in ACC that is often overexpressed via a MYB‑NFIB rearrangement. We hypothesized that AKT inhibition with the allosteric inhibitor MK‑2206 (MSD) can decrease MYB and induce tumor regressions in patients with incurable ACC. Patients with progressive, incurable ACC were enrolled. MK‑2206 150 mg weekly was given; escalation to 200 mg was allowed. The primary endpoint was confirmed response. Secondary endpoints were progression‑free survival (PFS), overall survival (OS), and safety. An exploratory analysis evaluating MK‑2206 impact on MYB expression was conducted in a subset of patients. Sixteen patients were enrolled; 14 patients were evaluable for efficacy. No confirmed responses were observed. Thirteen patients had stable disease and one had disease progression as best response. Median PFS was 9.7 months (95% CI: 3.8‑11.8) and median OS 18.0 months (95% CI: 11.8‑29.9). Nine of 16 (56%) patients had at least one grade 3 treatment‑related adverse event with the most common being rash (38%), fatigue (19%), decreased lymphocyte count (13%), and hyperglycemia (13%). Twelve of 14 tumors (86%) tumors had detectable MYB by immunohistochemistry; 7/14 (50%) had a MYB‑NFIB gene rearrangement. Serial biopsies revealed decreased MYB levels with MK‑2206 in 4 of 5 cases. MK‑2206 failed to induce clinical responses in patients with incurable ACC. AKT inhibition may diminish MYB protein levels, though the effect was highly variable among patients. Novel approaches to target MYB in ACC are needed.
ACC is a rare, aggressive malignancy that often lacks effective systemic options. This trial offers a targeted approach that may improve response rates while sparing normal tissues, potentially leading to better outcomes for patients with limited treatment choices.
Bizonyítékszint: Korai humán adat. Kis vagy feltáró emberi adat.
Kapcsolódó jelek
- Correction: Primary cutaneous adenoid cystic carcinoma of the right forearm: a case report and dermoscopic features
- A multiplex preclinical model for adenoid cystic carcinoma of the salivary gland identifies regorafenib as a potential therapeutic drug
- Deciphering the potential pathogeny of rare tracheal adenoid cystic carcinoma by single‑cell RNA‑sequencing
- Adenoid cystic carcinoma (ACC)
- DAY301 | Day One Biopharmaceuticals