PO.CT01.04 · 临床试验
IOB-032/PN-E40: A phase 2 study of neoadjuvant/adjuvant IO102-IO103 cancer vaccine plus pembrolizumab in resectable HNSCC
作者与单位
摘要 Abstract
IO102-IO103 is an investigational immune-modulatory therapeutic cancer vaccine targeting tumor and immune-suppressive cells in the tumor microenvironment (TME) via activation and expansion of T cells against IDO1 and PD-L1-positive cells. Perioperative administration of pembrolizumab (pembro) has demonstrated significant improvement in event-free survival (EFS) for patients (pts) with resectable head and neck squamous cell carcinoma (HNSCC). Here we test IO102-IO103 plus pembro in the perioperative setting. IOB-032/PN-E40 (NCT05280314) is an open-label, multi-cohort, Phase 2 trial evaluating safety, anti-tumor and immunological activity of IO102-IO103 plus pembro as neoadjuvant/adjuvant treatment. Pts with resectable HNSCC (stage III−IV), regardless of human papillomavirus (HPV) status, received IO102-IO103 and pembro every 3 weeks (Q3W) for 2 or 3 cycles followed by surgery and risk-based standard of care radiotherapy (RT) ± chemotherapy (chemo). After recovery, adjuvant treatment with IO102‑IO103 plus pembro was administered Q3W for up to 15 cycles. The primary endpoint is major pathological response (MPR; ≤10% residual viable tumor [RVT]) at surgery. Other key endpoints include: EFS, safety and vaccine-specific immune-responses. Between Dec 2023 and Nov 2024, 16 pts with resectable HNSCC (including 2 HPV- oropharyngeal carcinoma) were enrolled. All pts completed at least 2 cycles of neoadjuvant treatment. At data cutoff 18-Jul-2025, 13 (81.3%) pts had undergone surgery and were evaluable for centrally determined pathological response. Median time to surgery was 34 days (range 29−134) from the first neoadjuvant dose. One pt refused surgery but wished to stay on treatment; 1 pt progressed and became inoperable, and 1 pt withdrew consent prior to surgery. Of 13 evaluable pts, 3 (23.1%) had a pathological response with ≤50% RVT (pTR-2) by central review and 5 (38.5%) had a pathological response per investigator review; both assessed 1 (7.7%) pt as meeting the criteria for MPR (≤10%). At data cutoff, 11 (68.8%) pts received adjuvant therapy after RT ± chemo, 4 of whom received chemoRT. Two pts decided not to initiate adjuvant treatment. In total, 3 (18.8%) pts discontinued treatment due to adverse events; two of these were treatment-related (soft tissue edema, grade 3; injection-site lump, grade 1). EFS and analysis of treatment-associated changes in the TME will be presented, together with baseline characteristics including PD-L1 status. This is the first trial investigating an IDO1-PD-L1-immune-modulatory cancer vaccine plus anti-PD-1 therapy as perioperative treatment for HNSCC. The regimen was well-tolerated, and the implementation of neoadjuvant dosing and pathological assessment was feasible. Further follow-up will provide key insights into the potential benefit of adding IO102-IO103 to perioperative treatment with pembro.
利益披露 Disclosure
B. Burtness,
ALX Oncology, AstraZeneca, Clearview Health Partners, Coherus Biosciences Inc., Genentech, Genmab, IO Biotech, One Carbon, Pfizer, Rakuten, Takeda Pharmaceuticals Other, Consultant.
Answers in CME Other, Other.
Clinical Care Options LLC Other, Speaker.
GlaxoSmithKline Other, Consultant fees and research fees to self and institution.
Induxion Other, Consultant fees to self and institution.
Janssen Pharmaceuticals Other, Consultant fees and research fees to self and institution.
MedLearning Group Other, Speakers bureau or promotional education.
Merck and Merck KGaA Other, Consultant fees and research fees to self and institution.
Merus Other, Data & Safety Monitoring.
OncLive Other, Other.
PRIME Other, Speakers bureau or promotional education.
Up to Date Other, Other.
Yale School of Medicine Employment.
R. Uppaluri,
Merck Other, Travel, Consulting or Advisory Role.
Daichi-Sankyo Other, Research funding and consulting or Advisory Role.
Regeneron Consulting or Advisory Role.
Johnson & Johnson/Janssen Consulting or Advisory Role.
Washington University Other Intellectual Property, Washington University licenses mouse oral cancer cell lines made by my lab. I receive royalties from
Washington University from these agreements
.
IO Biotech Uncompensated Relationships.
M. J. Dennis, None.
A. M. Lim,
Pfizer uncompensated consultancy.
Eisai uncompensated consultancy.
Lilly uncompensated consultancy.
Merck Healthcare uncompensated consultancy.
Regeneron Pharmaceuticals Other, conference registration and support for an investigator initiated trial and translational research support from Regeneron Pharmaceuticals received by the institution.
Peter MacCallum Cancer Center Discovery Partner Fellowship Other, Supported.
R. A. Scolyer,
Pfizer Other, uncompensated consultancy.
Eisai Other, uncompensated consultancy.
Lilly Other, uncompensated consultancy.
Merck Healthcare Other, uncompensated consultancy.
Regeneron Pharmaceuticals Other, support for an investigator initiated trial and translational research support from Regeneron Pharmaceuticals received by the institution.
Peter MacCallum Cancer Center Discovery Partner Fellowship Other, supported.
E. Alesi, None.
A. Wakatsuki Pedersen,
IO Biotech Employment, Stock.
A. Wesa,
IO Biotech Employment, Stock.
R. K. Adapala,
IO Biotech Employment, Stock.
U. Kring Hansen,
IO Biotech Employment, Stock.
M. Iglesias,
IO Biotech Employment, Stock.
B. Wang,
IO Biotech Employment, Stock.
C. Abildgaard,
IO Biotech Employment, Stock.
Q. Ahmad,
IO Biotech Employment, Stock.
F. Ringeisen,
IO Biotech Employment, Stock.
G. V. Long,
Bayer Other, consultant advisor.
BioNTech Other, consultant advisor.
Boehringer Ingelheim Other, consultant advisor.
Bristol Myers Squibb Other, consultant advisor.
Byondis B.V. Other, consultant advisor.
Evaxion Other, consultant advisor.
Fortiva Biologics Other, consultant advisor.
GI Innovation Other, consultant advisor.
Hexal AG (Sandoz Company) Other, consultant advisor.
Highlight Therapeutics S.L. Other, consultant advisor.
Immunocore Other, consultant advisor.
Innovent Biologics USA Other, consultant advisor.
IO Biotech Other, consultant advisor.
Iovance Biotherapeutics Other, consultant advisor.
MSD Other, consultant advisor.
Novartis Other, consultant advisor.
Pierre Fabre Other, consultant advisor.
Regeneron Other, consultant advisor.
Scancell Other, consultant advisor.
SkylineDX B.V. and Strand therapeutics Other, consultant advisor.
R. I. Haddad,
Dana-Farber Cancer Institute Employment.
NCCN Other, leadership.
tosk Stock.
Merck, Eisai, AstraZeneca, GSK, EMD Serono, Bayer, Boehringer Ingelheim, ALX Oncology, aveo, Genmab, PDS Biotechnology, Scholar Rock, Genzyme, Johnson & Johnson/Janssen, RAPT Therapeutics, Abbvie Other, Consulting or Advisory Role.
Bristol-Myers Squibb/Celgene Consulting or Advisory Role.
Merck, Bristol-Myers Squibb, AstraZeneca, Genentech, Pfizer, Kura, EMD Serono, Incyte, Merus, AVEO, GlaxoSmithKline Other, Research funding for institution.
Nanobiotix, ISA Pharmaceuticals, Boehringer Ingelheim, Hookipa Pharma, Incyte Other, Other relationship.