Bempegaldesleukin (NKTR-214) With Radiation and Anti-PD-1 Immunotherapy for Head and Neck Squamous Cell Carcinoma

NCT04936841 | Terminated Phase 2 Results DMC FDA Drug

• 5 other identifiers: UW20092A533300SMPH/HUMAN ONCOLOGYProtocol Version 4/19/20212021-0141
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This trial will evaluate safety and efficacy of the combination of anti-PD1, NKTR-214, and palliative radiation therapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Twenty-four participants will be enrolled to evaluate the efficacy of this combination.

Conditions

Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is the percentage of participants whose cancer shrinks or disappears after treatment. ORR will include confirmed complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST1.1, by investigator assessment.

  up to 7 months (at Standard-of-care imaging 3 to 6 months after Cycle 1)

Secondary Outcomes (10)

• Number of Participants With Adverse Events Greater Than or Equal to Grade 3

  up to 14 months (study terminated early)

• Summary of Adverse Events Greater Than or Equal to Grade 3 by Count of Participants Who Experienced Them

  up to 14 months (study terminated early)

• Progression Free Survival (PFS)

  up to 14 months (study terminated early)

• Overall Survival (OS)

  up to 14 months (study terminated early)

• Number of Participants With Clinical Benefit (CB)

  up to 14 months (study terminated early)

Other Outcomes (4)

• Expression of PD-L1 by Histology

  up to 3 months

• Levels of IFN-γ Expressing and CD122+ T Cells in Peripheral Blood Mononuclear Cells (PBMC)

  up to 5 years

• Diversity and Clonality of the T Cell Receptor Repertoire by Deep Sequencing of PBMC

  up to 5 years

Study Arms (1)

NKTR-214, anti-PD therapy plus Palliative Radiation

EXPERIMENTAL

Cycle 1 consists of anti-PD-1 therapy (200mg) and NKTR-214 (0.006 mg/kg3 administered intravenously), followed by palliative radiation (8 Gy x 3 or 4 Gy x 5 fractions) combined with anti-PD-1 therapy and NKTR-214 in cycle 2. In subsequent cycles participants will receive NKTR-214 and anti-PD-1.

Drug: NKTR-214; Drug: anti-PD-1 therapy; Radiation: Palliative Radiation

Interventions

NKTR-214 DRUG

Bempegaldesleukin (NKTR-214) is an immunotherapeutic protein prodrug specifically designed to activate the patient's immune system for the treatment of cancer by providing a controlled, sustained signal to the interleukin-2 (IL-2) receptor pathway (pharmacological classification: immunostimulatory interleukin cytokine)

Also known as: bempegaldesleukin

NKTR-214, anti-PD therapy plus Palliative Radiation

anti-PD-1 therapy DRUG

immunotherapy drug, monoclonal antibody

Also known as: Pembrolizumab

NKTR-214, anti-PD therapy plus Palliative Radiation

Palliative Radiation RADIATION

radiation to relieve symptoms

NKTR-214, anti-PD therapy plus Palliative Radiation

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately
• Qualify for anti-PD-1 therapy based on current guidelines at the time of registration. This includes the standard requirement for the participant's tumor to have been previously determined to express PD-L1 with a combined positive score ≥ 1, as determined by an FDA-approved test.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 within 30 days prior to enrollment
• Histologically proven diagnosis of head and neck squamous cell carcinoma that is metastatic or recurrent disease that is surgically incurable
• Prior cancer treatment other than anti-PD-1 therapy must be completed at least 30 days prior to registration and the participant must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline. Participants may not undergo concurrent anti-cancer treatment during treatment with protocol therapies. This includes no treatment with growth factors, tyrosine kinase inhibitors, tumor-specific antibodies, or cytotoxic chemotherapies such as cisplatin. Participants who have previously or are currently taking an anti-PD-1 therapy are eligible for this study if they meet eligibility criteria 2. Participants who have previously taken any other immune checkpoint inhibitor are eligible as long as they have completed that treatment at least 30 days prior to registration and meet all other eligibility criteria.
• Participants with central nervous system (CNS) metastases are eligible if the CNS lesions are stable for at least 2 months and if tapered off treatment doses of systemic corticosteroids for at least 2 weeks prior to enrollment on the trial. Management with maintenance physiologic doses of corticosteroids (equivalent doses of prednisone ≤ 10 mg daily) is acceptable.
• Participants must have an "index" tumor that: 1) is deemed by the treating radiation oncologist to potentially benefit from palliative radiation 2) is amenable to biopsy, 3) is ≥ 1 cm in longest dimension.
• Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 30 days prior to enrollment
• White blood cell (WBC) ≥ 3,000/mm3
• Absolute Neutrophil Count (ANC) ≥ 1,500/mm3
• Hemoglobin (Hgb) ≥ 9 g/dL
• Platelets ≥ 100,000/mm3
• Serum creatinine ≤ 2.0 mg/dL
• Total Bilirubin ≤ 2.0 × upper limit of normal (ULN) (\< 3.0 for subjects with Gilbert's Syndrome)
• Aspartate aminotransferase (AST) ≤ 3 × ULN

You may not qualify if:

• Subjects with significant intercurrent illnesses per physician discretion
• Subjects with active or acute infections or active peptic ulcers, unless these conditions are adequately corrected or controlled, in the opinion of the treating physician
• Subjects with a diagnosed auto-immune disease (exceptions: subjects with controlled diabetes mellitus type I, thyroid disease, rheumatoid arthritis, vitiligo and alopecia areata not requiring treatment with immunosuppressants are eligible)
• Subjects with a history of diabetes mellitus requiring systemic therapy within the past 3 months (i.e. either oral hypoglycemic agents or insulin) must have a documented Hemoglobin A1c \< 8.0 % within 90 days of registration.
• Subjects with known genetic conditions causing pre-disposition to radiotherapy (RT) toxicity (i.e.: Li-Fraumeni, ATM deficiency, active scleroderma, etc.)
• Participants with a prior diagnosis of cerebrovascular accident (CVA) or transient ischemic attack (TIA)
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)
• Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least three years prior to enrollment
• Prolonged Fridericia's corrected QT interval (QTcF) \> 450 ms for men and \> 470 ms for women at time of enrollment
• Subjects with symptoms of ischemic cardiac disease, congestive heart failure, or myocardial infarction within 6 months of registration and/or uncontrolled cardiac rhythm disturbance
• Subjects with a pulmonary embolism, deep vein thrombosis, or prior clinically significant venous or non-CVA/TIA arterial thromboembolic event (e.g., internal jugular vein thrombosis) within 3 months prior to enrollment
• Patients with a history of a venous or arterial thromboembolic event must be asymptomatic prior to enrollment and must be receiving a stable regimen of therapeutic anticoagulation (low molecular weight heparin (LMWH) or direct oral anticoagulation (DOAC)). Use of coumadin is permitted; however, therapeutic dosing should target a specific international normalized ratio (INR) stable for at least 4 weeks prior to enrollment. NKTR-214 has the potential to down-regulate metabolizing enzymes for coumadin for approximately 1 week after administration of each dose of NKTR-214. Due to the possibility of drug-drug interactions between coumadin and NKTR-214, frequent monitoring of INR and ongoing consideration of dose adjustments are warranted throughout the patient's participation on study.
• Subjects with significant psychiatric disabilities or seizure disorders if considered unsafe in the opinion of the treating physician
• Subjects with symptomatic pleural effusions or ascites
• Subjects with organ allografts

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• Nektar Therapeutics: collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

bempegaldesleukin; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Limitations and Caveats

Study terminated early by the sponsor

Results Point of Contact

• Title: Zachary Morris, MD, PhD
• Organization: University of Wisconsin School of Medicine and Public Health

zmorris@humonc.wisc.edu

(608) 263-2603

Study Officials

• Zachary Morris, MD, PhD

  University of Wisconsin, Madison

  STUDY CHAIR

• Paul Harari, MD

  University of Wisconsin, Madison

  STUDY CHAIR

• Adam Burr, MD, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

• Justine Bruce, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: June 10, 2021
• First Posted: June 23, 2021
• Study Start: August 5, 2021
• Primary Completion: October 4, 2022
• Study Completion: October 4, 2022
• Last Updated: April 4, 2024
• Results First Posted: April 4, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)