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

NCT03325465 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: IRB17-0993
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

squamous cell carcinoma of the head and neck; head and neck cancer; neoadjuvant pembrolizumab; epacadostat

Outcome Measures

Primary Outcomes (2)

• Rate of major treatment effect (rate of treatment response)

  MTE will be assessed in the same way as done by Uppaluri et al (Uppaluri ASCO 2017) upon pathologic review and assessment of 50% resolution of tumor with active immune response (termed "major treatment effect" in their study).

  3-4 weeks after patient has begun treatment

• Rate of complete response

  Response rate at surgery compared to historic data with chemotherapy

  8 weeks after patient has begun treatment

Secondary Outcomes (4)

• Progression free survival rate

  From the start of treatment to the first documented report of disease progression or death, whichever comes first, not to exceed 100 months.

• Overall survival rate

  From the start of treatment to the time of death, not to exceed 100 months.

• Number of patients with adverse events prior to and after surgery

  Up to 2 years

• Complete response rate

  From the start of treatment to the first documented report of response, disease progression, or death, whichever comes first, not to exceed 100 months.

Study Arms (1)

Pembrolizumab and epacadostat

EXPERIMENTAL

Patients will receive neoadjuvant immunotherapy either with anti-PD-1 (pembrolizumab) alone or anti-PD-1 in combination with IDO1 inhibition (epacadostat). Patients will receive Pembrolizumab every 3 weeks over a period of 8 weeks as well as epacadostat 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).

Drug: Pembrolizumab; Drug: Epacadostat

Interventions

Pembrolizumab DRUG

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.

Also known as: Keytruda

Pembrolizumab and epacadostat

Epacadostat DRUG

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.

Pembrolizumab and epacadostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be 18 years of age or older on day of signing informed consent.
• Patients with non-bulky/non-bulky squamous cell carcinomas of the head and neck, with an indication for surgical therapy.
• T1N1-N2B, T2-4N0-N2b stage are generally eligible
• If determined per tumor board that a low-volume/non-bulky tumor of another stage is appropriate for resection (e.g. small volume T4 with a small amount of bone invasion) such tumors may also be considered for this study if recommendation in tumor board is such.
• Be appropriate candidates for resection and curative intent therapy in general.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Consent to undergo biopsy from a newly obtained core or excisional biopsy of a tumor lesion before study drug administration, and during treatment. Biopsy in case of progressive disease is optional.
• Ability to swallow tablets (at future point administration via G-tube may be allowed if approved by drug manufacturer)
• Measurable disease per RECIST 1.1.
• Known HPV status for oropharyngeal primary tumors.
• Pre-operative scans including MRI/CT neck and, CT chest with contrast. If contrast is contraindicated, Staging PET or PET-CT is acceptable although high quality / diagnostic cross-sectional imaging of the head and neck area is recommended.
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
• Table 1 Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) Renal Serum creatinine OR within upper limit of normal (ULN) OR
• Measured or calculateda creatinine clearance ≥60 mL/min for subject with creatinine (GFR can also be used in place of creatinine or levels \> institutional ULN CrCl)

You may not qualify if:

• Has a diagnosis now or in the past of immunodeficiency requiring systemic steroid therapy in excess of physiologic dose (or any other form of immunosuppressive therapy within 10 days prior to the first dose of trial treatment).
• Has bulky tumor (define as N3 lymph node or equivalent lymph conglomerate (≥ 6 cm in one dimension), or primary tumor \> 4 cm). Cystic HPV+ lymph nodes should be assessed in tumor board and may not be considered bulky.
• Has a known history of active TB (Bacillus Tuberculosis).
• Other life-threatening illness that is expected to impact life expectancy within 3 years.
• Hypersensitivity to pembrolizumab, epacadostat or any of its excipients.
• Has a known additional malignancy that was diagnosed within the last five years that is either progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, or in a broader sense is not felt to impact life-expectancy.
• Has active autoimmune disease that has required systemic (large physiologic dose) treatment in the past year (i.e. with use of disease modifying agents, corticosteroids or any other immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic immunosuppressive treatment.
• History of non-infectious pneumonitis requiring steroids or current pneumonitis
• Has an active viral infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• Has received a live vaccine within 30 days of planned start of study therapy.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

pembrolizumab; epacadostat

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Study Officials

• Tanguy Seiwert, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2017
• First Posted: October 30, 2017
• Study Start: January 22, 2018
• Primary Completion: November 7, 2018
• Study Completion: November 7, 2018
• Last Updated: April 22, 2019

Record last verified: 2019-04

Locations

US (1)