Abstract
Nanoparticle albumin-bound (nab) paclitaxel in combination with nivolumab as treatment of recurrent or metastatic head and neck squamous-cell carcinoma (RM-HNSCC) that progressed on a PD-1 inhibitor: A single-arm, phase 2 trial.
Author
person
Jared Cohen
Washington University Siteman Cancer Center, St. Louis, MO
info_outline
Jared Cohen, Peter John Oppelt, Sarah Pennock, Jingxia Liu, Jessica C. Ley, Douglas Adkins
Full text
Authors
person
Jared Cohen
Washington University Siteman Cancer Center, St. Louis, MO
info_outline
Jared Cohen, Peter John Oppelt, Sarah Pennock, Jingxia Liu, Jessica C. Ley, Douglas Adkins
Organizations
Washington University Siteman Cancer Center, St. Louis, MO, Washington University School of Medicine, St. Louis, MO
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
Bristol-Meyers Squibb, Generous support from Gregory Stubblefield and Nancy Apel
Background:
Drugs bound to albumin selectively target cancer cells with upregulated macropinocytosis, an endocytic nutrient-scavenging process driven by constitutive hyper-activation of the EGFR, RAS, PIK3CA and Syndecan1 signaling pathways that frequently occur in HNSCC.
nab
-paclitaxel is an active drug in HNSCC and has immunologic effects that can prime an immune response to PD-1 inhibitors, potentially reversing resistance to these agents. These effects include decreased TREGs, increased pro-inflammatory macrophages and differentiation of MDSC to dendritic cells, increased HLA class I expression and antigen presentation, and recruitment of CD8+ CTLs into tumor.
Methods:
In a single-arm phase 2 trial, patients with RM-HNSCC that progressed on a PD-1 inhibitor received 28-day cycles of
nab-
paclitaxel (125 mg/m
2
IV days 1, 8, and 15) and nivolumab (480 mg IV day 1). Treatment continued until discontinuation criteria were met. The primary endpoint was objective response, assessed with RECIST1.1 by an independent radiologist. The primary hypothesis was that this regimen would result in a higher objective response rate (ORR) than historically reported with standard chemotherapy or cetuximab in similar patients. A Simon optimal two-stage design tested the null hypothesis (H
0
: ORR≤30%) versus the alternative hypothesis (H
1
: ORR=50%) at the type I error rate of 5% and power 0.80. In the first stage, 15 patients were to be accrued. If ≥6 responses occurred, 31 additional patients were to be accrued. The null hypothesis will be rejected if ≥19 responses are observed in these 46 patients. We report the results of the primary endpoint for the first stage of the trial.
Results:
15 evaluable patients enrolled into the first stage of the trial. Key tumor characteristics and prior treatment history included HPV status (positive: 8; negative: 7), PD-L1 status (CPS 1-19: 7; ≥20: 8), # of lines of prior systemic treatment for RM disease (1-2: 12; ≥3: 3), interval (months) from prior PD-1 inhibitor (<6: 11; ≥6: 4), duration (months) on prior PD-1 inhibitor (median: 6, range: 1-16), and best response to prior PD-1 inhibitor (PR: 4; SD: 6; PD: 5). Tumor response to
nab-
paclitaxel and nivolumab occurred in 7 of 15 patients (ORR 47%). The best tumor response was PR (7), SD (5) and PD (3).
Conclusions:
Among patients with RM-HNSCC that progressed on a PD-1 inhibitor, the ORR with
nab
-paclitaxel and nivolumab was 47% during the first stage of the phase 2 trial. Enrollment to the second stage is ongoing. Clinical trial information: NCT04831320.
Clinical status
Clinical
1 clinical trial
2 organizations
2 drugs
7 targets
Clinical trial
Nab-Paclitaxel in Combination With Nivolumab to Treat Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma That Progressed on a PD-1 or PD-L1 Inhibitor: A Single-Arm, Phase 2 TrialStatus: Active (not recruiting), Estimated PCD: 2024-12-31
Drug
AbraxaneDrug
nivolumabTarget
PD-1Target
RAS/BRAFTarget
TREGsTarget
CD8+ CTLsTarget
PIK3CATarget
Syndecan1