Trial of Cemiplimab, or Cemip-Chemo Followed by Biomarker-guided Treatment for Pts w/HPV H&N Ca

NCT04988074 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: J20118IRB00259330
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

To determine if it is feasible to use neoadjuvant immunotherapy (or immunotherapy plus chemotherapy) to reduce treatment intensity and improve long-term quality of life while maintaining very high cure rates.

Conditions

HPV-Related Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (5)

• 2-year progression free survival rate

  Up to 2 years

• Change in Quality of life as measured by MD Anderson Dysphagia Inventory (MDADI)

  The MD Anderson Dysphagia Inventory (MDADI) is a 20 item quality of life instrument specifically focusing on swallowing. The total score ranges from 20 to 100 with the higher score indicating higher level of function. Each item is scored on a 5 point Likert scale (strongly disagree, disagree, no opinion, agree, strongly agree).

  Up to 2 years

• Change in quality of life as measured by the Sydney Swallow Questionnaire (SSQ).

  The SSQ consists of 17 questions, (16 visual analogue scales (VAS) and one question scored on a Likert scale (0-5). The score for each VAS question is the distance in mm from the origin (left extremity) to the patient's mark on the visual analogue scale. The total score is calculated by summing the 16 individual VAS scores and the Likert scale (0-5) multiplied by 20. Thus converting the range of possible scores for Likert question from 0-5 to 0-100, consistent with the remaining 16 questions, to yield a total score out of a possible maximum of 1700. Higher scores indicate higher symptomatic severity of oral-pharyngeal dysphagia.

  Up to 2 years

• Change in swallow function as measured by the Sydney Swallow Questionnaire (SSQ).

  Desirable swallowing function at 1 year for this study will be defined as SSQ ≤ 250 and MDADI ≥ 70

  Up to 2 years

• Change in swallow function as measured by the MD Anderson Dysphagia Inventory.

  Desirable swallowing function at 1 year for this study will be defined as SSQ ≤ 250 and MDADI ≥ 70

  Up to 2 years

Secondary Outcomes (6)

• To determine 2-year overall survival (OS) for the entire cohort

  From the date of registration to the date of death or date of last follow-up, up to 2 years

• To determine 2-year rates of locoregional and distant control for the entire cohort

  Time of registration to time of disease progression in head and neck or below clavicles for distant failure, assessed up to two years

• Number of grade 3 toxicities

  100 days after last dose of study drug(s).

• Number of grade 4 toxicities

  100 days after last dose of study drug(s).

• Number of grade 3 Immune-related adverse events (irAE)

  100 days after last dose of study drug(s).

Other Outcomes (3)

• Rate of Induction Tumor/HPV

  Neoadjuvant therapy to local therapy, approximately 9 weeks

• HPV ctDNA Clearance

  Up to 18 months post locoregional therapy

• To interrogate the immune micro-environment at baseline, and 3 weeks into induction therapy with cemiplimab and chemotherapy based on an on-treatment biopsy

  neoadjuvant treatment, up to 3 weeks

Study Arms (2)

De-Escalated Therapy

EXPERIMENTAL

Surgery (TORS) or Low-dose Radiation Therapy (42 Gy)

Drug: Cemiplimab

Non/Minimally De-Escalated Therapy

EXPERIMENTAL

Surgery + Post-Operative Radiation Therapy (PORT) or 60 Gy Chemo-Radiation Therapy (CRT)

Drug: Cemiplimab

Interventions

Cemiplimab DRUG

Cemiplimab for 9 weeks +/- Carboplatin + Paclitaxel

Also known as: LIBTAYO

De-Escalated Therapy; Non/Minimally De-Escalated Therapy

Eligibility Criteria

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

You may qualify if:

• Subjects must have pathologically confirmed HPV-positive head and neck squamous cell carcinoma of the oropharynx. Confirmed HPV-positive disease of other subsites are uncommon but also eligible.
• HPV testing must be compliant with the following criteria:
• p16 IHC positivity is sufficient to enroll and initiate treatment (p16 IHC interpretation to follow guidelines by Jordan and Lingen et al89).
• p16 IHC positivity is to be validated using an HPV nucleic acid based secondary assay (HPV ISH, HPV PCR, HPV cfDNA) before or during the neoadjuvant phase.\*
• HPV DNA ISH is acceptable if positive, however a negative HPV DNA ISH should be confirmed by HPV RNA ISH or other nucleic acid based method.
• HPV16 type (non-HPV16 related cancers are not eligible)\*
• \*In the rare event that a subject starts treatment based on p16 IHC alone and HPV type determination is not yet available, subject may commence neoadjuvant treatment based on p16 IHC alone, as along as HPV nucleic acid testing is pending. Patients with non-HPV16 associated tumors will have to leave the study. Given the prevalence of HPV16 (\~90-95%) and usual rapid turnaround of HPV16 RNA-ISH (other assays) this is not expected, but the primary goal is not to have unnecessary treatment delay for subjects.
• Availability of ≥8 unstained 5 micron slides. Subjects who cannot fulfill this requirement will need to undergo a new biopsy prior to enrollment on study. In patients where biopsy is not safe, or logistically feasible this requirement can be waived by the PI or a lower number of slides can be accepted.
• Subjects must be at least 18 years of age.
• AJCC 7th edition: Stage III, IV without bulky N2b/c disease (defined as N3 equivalent volume) and without bulky T4 (≤30cc).
• (AJCC 8th edition: Stage II or III, or stage I with N1 or N2 nodes (\>3cm or multiple), without bulky nodal disease (defined as N3 equivalent volume) and without bulky T4 disease (defined as 30cc tumor volume)).
• Measurable disease (either primary site and/or nodal disease) by RECIST 1.1 criteria.
• No previous radiation or chemotherapy for a head and neck cancer.
• No complete surgical resection for a head and neck cancer within 8 weeks of enrollment (although lymph node biopsy including excision of an individual node with presence of residual nodal disease, or surgical biopsy/excision of the tumor with residual disease is acceptable).
• ECOG performance status 0-1 (Karnofsky ³70%).

You may not qualify if:

• Unequivocal demonstration of distant metastases (M1 disease).
• Unidentifiable/unknown primary site (neither imaging nor exam nor biopsy can identify the primary). Treating physicians should agree that the primary is sufficiently identified to proceed with clinical care/treatment (e.g. in the case of imaging localization, but absence of biopsy proven pathology)
• Intercurrent medical illnesses which would impair subject tolerance to therapy or limit survival. Including but not limited to ongoing or active infection, immunodeficiency, symptomatic congestive heart failure, pulmonary dysfunction, cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance. Once clinically stable, as defined by the PI, they are eligible.
• Prior surgical therapy other than incisional/excisional biopsy or organ-sparing procedures such as debulking of airway-compromising tumors. Residual measurable tumor is required for enrollment on study as outlined above
• Subjects receiving other investigational agents.
• Peripheral neuropathy \>grade 1
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy in excess of physiologic dose or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active tuberculosis (Bacillus Tuberculosis infection)
• Has hypersensitivity to cemiplimab or any other drug used in this protocol.
• Has had a prior systemic anti-cancer treatment within the last 8 weeks
• Has a known additional malignancy that is 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 thyroid cancers, any tumors that are not likely to influence life expectancy in the subsequent 3 years without active treatment other than hormonal therapies (e.g., adjuvant after breast cancer, or low grade prostate cancer).
• Has active autoimmune disease that has required systemic treatment in the past year (i.e., with use of steroids or immunosuppressive drugs). Replacement therapy e.g., levothyroxine, insulin, or physiologic corticosteroid doses for adrenal or pituitary insufficiency, etc. are not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has a history of Human Immunodeficiency Virus (HIV) (HIV ½ antibodies).
• Has known active Hepatitis B (e.g., HbsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). However, if eradicated subject is eligible.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

MeSH Terms

Interventions

cemiplimab

Study Officials

• Nyall R London, M.D.

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zubair Khan, M.D.

CONTACT

410-955-3157; zkhan@jhmi.edu

Sydjea Stillwell, R.N.

CONTACT

410-614-9231; sstillw1@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2021
• First Posted: August 3, 2021
• Study Start: December 13, 2021
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 3, 2026

Record last verified: 2026-02

Locations

US (1)