NCT03325465

Neoadjuvant Pembrolizumab + Epacadostat Prior to Curative Surgical Care for Squamous Cell Carcinoma of the Head and Neck

Neoadjuvant Pembrolizumab + Epacadostat Prior to Curative Surgical Care for Squamous Cell Carcinoma of the Head and Neck (SCCHN): The KEO Trial

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: University of Chicago · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The KEO study is a single arm phase II trial including 44 patients with T1N1-2B, T2N0-N2B head and neck squamous cell carcinoma (HNSCC) eligible for curative-intent resection (+/- adjuvant therapy), who receive neo-adjvuant pembrolizumab + epacadostat. The primary objective of this study is to determine rate of major treatment effect (MTE) to neoadjuvant pembrolizumab+epacostat immunotherapy in SCCHN compared to historic data with neoadjuvant pembrolizumab alone.

Detailed description

The KEO study is a single arm phase II trial including 44 patients with T1N1-2B, T2N0-N2B head and neck squamous cell carcinoma (HNSCC) eligible for curative-intent resection (+/- adjuvant therapy), who receive neo-adjvuant pembrolizumab + epacadostat. Patients that fit the inclusion criteria (see detailed eligibility criteria below) will receive neoadjuvant immunotherapy either with anti-PD-1 (pembrolizumab) alone or anti-PD-1 in combination with IDO1 inhibition (epacadostat). Patients will receive 200 mg IV Pembrolizumab every 3 weeks for up to 3 doses over a period of 8 weeks as well as oral epacadostat 100 mg BID starting on day 1 for the duration of pembrolizumab treatment. All patients will undergo baseline biopsy (mandatory, sampling ≥ 4 areas to represent the tumor), as well as baseline imaging (and for exploratory analysis collection of blood for baseline ctDNA testing and TCR analysis). Patients who are unable to safely (or for other reasons unwilling to undergo biopsy at baseline and on treatment 3-4 weeks in for infiltrate assessment are not eligible for the study. MRI is the preferred imaging modality; however, diagnostic CT is acceptable if patient is unable to undergo MRI or as clinically indicated. Subsequently at week 3-4 an interim assessment will be performed: 1. All patients will undergo imaging with a 2nd MRI scan (or CT, to match prior imaging). 2. All patients will also undergo repeat mandatory on-treatment biopsy consisting of of 4-6 representative samples to compare to the baseline biopsy. Adequacy of response to treatment will be assessed in assessing eradication of tumor/presence of antitumor tumor response (analogous to reports in lung cancer (Forde et al ESMO 2016). The on-treatment biopsy is essential in the assessment of early response and decision to extend neo-adjuvant treatment to 8 weeks is based in large part on this biopsy. In patients where an on-treatment biopsy is not obtained (e.g no longer considered safe or status of patient has changed), patients will automatically be considered non-complete responders, and take off study after 4 weeks (with the very unlikely but possible exceptions of complete response radiologic response at 4 weeks imaging). 3. For exploratory purposes, blood will also be drawn for repeat ctDNA and TCR analysis in order to assess potential suitability of dynamic changes ctDNA or TCR clonality/diversity as candidate biomarkers for follow-up studies. At the week 3/4 interim assessment, results of the imaging and biopsy will be used to determine response and to determine continuation of immunotherapy induction treatment for up to 8 weeks (full immunotherapy induction course). Patients that demonstrate stable disease or tumor shrinkage radiographically and biopsy demonstrating dense lymphocytic infiltrate with dying tumor / decrease in residual viable tumor will continue on protocol. Those patients with lack of lymphocytic infiltrate/dying tumor or increasing tumor on radiology (and confirmed on pathology from 2nd biopsy) will be transitioned to standard of care treatment with early salvage surgery or chemoradiation (as clinically indicated). Pre-surgery assessment: For those patients continuing - a second confirmatory scan will be done 3-4 weeks later again coupled with a blood draw, and followed by surgery at/around week 8 (+/-1 week depending on operating schedules). Definitive surgery will be done at week 8. Surgical specimens will again be evaluated for percentage residual viable tumor and inflammatory infiltrate. Patients that exhibit complete pathologic response (no viable tumor) will follow close observation with repeat imaging (CT/MRI at 4-6 weeks), clinical exams and a PET scan at 12 weeks post-surgery (as well as serial ctDNA draws (exploratory). Patients with major pathologic responses (≤10% residual tumor, but tumor present) will be treated with de-escalated adjuvant radiation therapy as determined by the tumor board/radiation oncology. Patients with a surgical specimen that demonstrates \>10% residual tumor after surgery will undergo standard adjuvant RT/CRT as indicated. Adjuvant Phase: Patients will continue adjuvant pembrolizumab plus epacadostat every 3 weeks for 12 months and be monitored with ctDNA and imaging.

Conditions

• Squamous Cell Carcinoma of the Head and Neck

Interventions

Type	Name	Description
DRUG	Pembrolizumab	Patients will receive pembrolizumab alone or pembrolizumab in combination with epacadostat. Pembrolizumab will be administered at 200 mg IV every 3 weeks for up to 3 doses for no longer than 8 weeks prior to surgery. After surgery, patients will continue pembrolizumab plus epacadostat every 3 weeks for 12 months.
DRUG	Epacadostat	Patients will receive epacadostat in combination with pembrolizumab. Epacadostat will be administered orally at a dose of 100 mg twice a day starting on day 1 for the duration of pembrolizumab treatment. Patients will continue on this combination for no longer than 8 weeks prior to surgery. After surgery, patients will continue pembrolizumab plus epacadostat every 3 weeks for 12 months.

Timeline

• Start date: 2018-01-22
• Primary completion: 2018-11-07
• Completion: 2018-11-07
• First posted: 2017-10-30
• Last updated: 2019-04-22

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study