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568 Phase 2 trial of induction and concomitant CTLA4 (ipilimumab) and PD-1 (nivolumab) immune checkpoint blockade and intensity modulated radiation therapy (IMRT) in HPV-positive oropharyngeal squamous cell carcinoma (HPV-OPSCC)
  1. Maura Gillison,
  2. Michelle Williams,
  3. Jason Johnson,
  4. Cheuk Leung,
  5. Jay Reddy,
  6. Adam Garden,
  7. Renata Ferrarotto,
  8. Frank Mott,
  9. Xiuning Le,
  10. Gary Gunn,
  11. Anna Lee,
  12. Clifton Fuller,
  13. Charles Lu,
  14. Amy Moreno,
  15. Katherine Hutcheson,
  16. Neil Gross,
  17. Miriam Lango,
  18. Ryan Goepfert,
  19. Jeffrey Myers,
  20. Ehab Hanna,
  21. Weihong Xiao,
  22. Bo Jiang,
  23. Nils-Petter Rudqvist,
  24. Jack Lee and
  25. Jack Phan
  1. The University of Texas MD Anderson Cancer Center, Houston, TX, United States


Background PD-1 immune checkpoint blockade (ICB) improves survival versus chemotherapy in PD-L1 CPS≥1 recurrent or metastatic head and neck cancer. We evaluated the safety and efficacy of induction and concurrent CTLA4 and PD-1 ICB and IMRT in newly diagnosed HPV-OPSCC.

Methods PD-L1 CPS≥1, p16-positive + HPV RNA-Scope-positive, AJCC 8th edition T1-3N1-2 M0 or T3N0M0 OPSCC patients irrespective of smoking status received two, six-week cycles of ipilimumab (1 mg/kg) day 1 and nivolumab (3 mg/kg) on days 1, 15, and 29, and IMRT concurrent with cycle 2. IMRT was delivered in 4 weeks to pre-induction tumor volume (40-44 Gy) and one adjacent uninvolved nodal level (36 Gy). Post-induction volume was boosted to 50-66 Gy in 2 weeks. Response was evaluated by RECIST 1.1. Principal outcomes were FDG-PET complete response (PET-CR) at 6 months per Hopkins Criteria1 and progression-free survival (PFS) at 2-years. Correlatives included histological (% tumor viability)2 and molecular (plasma cfHPV clearance) responses after induction ICB.

Results Treated patients (35) were male (97%), median age 64 (49-78) years with stage T1(14), T2(16), T3(5) and N0(1), N1(33), N2(1) base of tongue (18) or tonsil (17) SCC. 66% had acute grade≥3 AEs (table 1). Five discontinued ICB due to toxicity (n=3), progression (n=1), or physician decision (n=1) and received concurrent platinum (n=3) or IMRT alone (n=2). PET-CR was 90% (29 of 32 evaluable). One of 3 patients without PET-CR progressed. After median follow-up of 14.9 months, 3 patients had local progression and were treated with surgery or SBRT. All patients are alive without cancer at last follow-up. Response to induction ICB was 14% (figure 1). Among 27 evaluable patients, histological response was 0% viability in 37% and <10% viability in 48% (figure 2). 96% had pathological treatment effect ≥20% [2]. At baseline, 97% were positive and 74% quantifiable (≥16 copies/ml) by cfHPV. cfHPV clearance was 30% after induction ICB and 100% 4 weeks after IMRT. Compared to standard planning, RT volume to ≥66 Gy and ≥50 Gy was reduced by 21% (+/- 3%) and 36% (+/- 4%), and dose to ipsilateral parotid, spinal cord, larynx and esophagus was reduced by up to 50%.

Conclusions Patients with HPV-OPSCC treated with induction and concurrent CTLA4 and PD-1 ICB with dose-volume-adapted IMRT experienced a 6-month PET-CR of 90%, a 2-year PFS of 86%, and acute grade≥3 toxicity rate of 66%. Efficacy of induction ICB was supported by <10% tumor viability in 48% and cfHPV clearance in 30%.

Acknowledgements Funded by Cancer Prevention and Research Institute of Texas and Bristol-Myers-Squibb.

Trial Registration NCT03799445


  1. Marcus C, et al. Head and neck PET/CT: therapy response interpretation criteria (Hopkins Criteria)-interreader reliability, accuracy, and survival outcomes. J Nucl Med 2014;55, 1411–6.

  2. Wise-Draper, et al. Phase II Clinical Trial of neoadjuvant and Adjuvant Pembrolizumab in Resectable Local-Regionally Advanced Head and Neck Squamous Cell Carcinoma. Clin Cancer Res 2022;28, 1345–1352.

Ethics Approval The study was approved by The University of Texas MD Anderson Cancer Center Institutional Review Board, approval numbers 2018-0381 and PA19-0470. All participants gave their informed consent prior to enrollment.

Abstract 568 Table 1

Grade=3 treatment related adverse events per CTCAE V4 that occurred after dose of ICB

Abstract 568 Figure 1

Waterfall plot of percent reduction in tumor volume by RECIST 1.1 after induction ICB

Abstract 568 Figure 2

Waterfall plot of percent reduction in tumor viability from baseline. Percent change in tumor viability (%, y-axis) in core needle biopsy at baseline versus 3-5 weeks on induction ICB. Due to tumor viability of 90-100% at baseline, patients with =95% and =90% change in viability achieved complete (i.e., 0% viability) and major* (i.e., <10% viability) histological response, respectively. RECIST response, partial (green), stable (blue), progression (red)

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