Open AccessA WIN Consortium phase I study exploring avelumab, palbociclib, and axitinib in advanced non‐small cell lung cancer
Author(s) -
Solomon Benjamin,
Callejo Ana,
Bar Jair,
Berchem Guy,
Bazhenova Lyudmila,
Saintigny Pierre,
Wunder Fanny,
Raynaud Jacques,
Girard Nicolas,
Lee J. Jack,
Sulaiman Raed,
Prouse Bruce,
Bresson Catherine,
Ventura Hila,
Magidi Shai,
Rubin Eitan,
Young Brandon,
Onn Amir,
LeylandJones Brian,
Schilsky Richard L.,
Lazar Vladimir,
Felip Enriqueta,
Kurzrock Razelle
Publication year - 2022
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.4635
Subject(s) - medicine , avelumab , axitinib , palbociclib , oncology , neutropenia , lung cancer , pembrolizumab , adverse effect , cancer , gastroenterology , immunotherapy , chemotherapy , breast cancer , sunitinib , metastatic breast cancer
Background The Worldwide Innovative Network (WIN) Consortium has developed the Simplified Interventional Mapping System (SIMS) to better define the cancer molecular milieu based on genomics/transcriptomics from tumor and analogous normal tissue biopsies. SPRING is the first trial to assess a SIMS‐based tri‐therapy regimen in advanced non‐small cell lung cancer (NSCLC). Methods Patients with advanced NSCLC (no EGFR , ALK , or ROS1 alterations; PD‐L1 unrestricted; ≤2 prior therapy lines) received avelumab, axitinib, and palbociclib (3 + 3 dose escalation design). Results Fifteen patients were treated (five centers, four countries): six at each of dose levels 1 (DL1) and DL2; three at DL3. The most common ≥Grade 3 adverse events were neutropenia, hypertension, and fatigue. The recommended Phase II dose (RP2D) was DL1: avelumab 10 mg/kg IV q2weeks, axitinib 3 mg po bid, and palbociclib 75 mg po daily (7 days off/21 days on). Four patients (27%) achieved a partial response (PR) (progression‐free survival [PFS]: 14, 24, 25 and 144+ weeks), including two after progression on pembrolizumab. Four patients attained stable disease (SD) that lasted ≥24 weeks: 24, 27, 29, and 64 weeks. At DL1 (RP2D), four of six patients (66%) achieved stable disease (SD) ≥6 months/PR (2 each). Responders included patients with no detectable PD‐L1 expression and low tumor mutational burden. Conclusions Overall, eight of 15 patients (53%) achieved clinical benefit (SD ≥ 24 weeks/PR) on the avelumab, axitinib, and palbociclib combination. This triplet showed antitumor activity in NSCLC, including in tumors post‐pembrolizumab progression, and was active at the RP2D, which was well tolerated. NCT03386929 clinicaltrial.gov