AzTrials
AzTrials

Head and Neck CancerPhase 2NCT04936841

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

A Phase 2 study testing NKTR-214, anti-PD-1 therapy and Palliative Radiation in people with Head and Neck Cancer, run by University of Wisconsin, Madison at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Cancer
What is being tested?
NKTR-214, anti-PD-1 therapy and Palliative Radiation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
1 siteUnited States
Study dates
5 Aug 2021to 4 Oct 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 18Show fewer
  • 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
  • Alanine aminotransferase (ALT) ≤ 3 × ULN
  • Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to enrollment and must agree to use effective contraception during active treatment and for 5 months after last dose of pembrolizumab and/or NKTR-214. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for ≥ 12 consecutive months.
  • As determined by the enrolling physician or protocol designee, ability of the participant to understand and comply with study procedures for the entire length of the study

Who cannot join

  • 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)
Show all 17Show fewer
  • 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
  • Subjects who require, or are likely to require, systemic treatment doses of corticosteroids, or other immunosuppressive drugs, or have used them within 2 weeks of registration (clarification: subjects receiving physiologic maintenance or replacement doses of systemic steroids or inhaled steroids are eligible)
  • Subjects with known human immunodeficiency virus (HIV) infection, active or chronic hepatitis B or hepatitis C infection, or with clinical evidence of hepatitis 15. Subjects with known hypersensitivity to IL2 or those who experienced significant immune-related AEs requiring treatment with steroids or other immunosuppressant therapy during prior treatment with ipilimumab, or anti- PD-1/PD-L1 checkpoint blockade therapy 16. Subjects who cannot provide independent, legal, informed consent

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Wisconsin

    Madison, Wisconsin, 53792

Other trials in United States

About this study

Official title: Phase II Study of Bempegaldesleukin (NKTR-214) Together With Palliative Radiation and Anti-PD-1 Checkpoint Blockade in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

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.

Read the detailed description

Following an informed consent process, participants will receive anti-PD-1 therapy with 200 mg of pembrolizumab and NKTR-214 at 0.006 mg/kg. Palliative radiation therapy will then be delivered to tumor sites causing or felt by the treating physician to have a high potential for causing symptoms with either 8 Gy X 3 or 4 Gy X 5 completed 3 to 7 days prior to cycle 2 of anti-PD1 and NKTR-214. Combined anti-PD-1 and NKTR-214 will then be delivered each subsequent cycle.

Efficacy will be measured by overall response rate (ORR), progression free survival (PFS), overall survival (OS), clinical benefit (CB), and duration of response with ORR the primary outcome being compared to historical control data. Toxicity will be evaluated prior to administration of each 21-day cycle, while receiving NKTR-214 followed by every four months after the participant is off trial. Health related quality of life questionnaires will be completed with cycle 1 and 2 and then every 4 cycles thereafter.

Being tested
NKTR-214, anti-PD-1 therapy, Palliative Radiation
Medical subject headings
Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NKTR-214Drug

    Also called bempegaldesleukin

    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)

  • anti-PD-1 therapyDrug

    Also called Pembrolizumab

    immunotherapy drug, monoclonal antibody

  • Palliative RadiationRadiation

    radiation to relieve symptoms

Study groups in NCT04936841
Study groupRoleWhat they receive
NKTR-214, anti-PD therapy plus Palliative RadiationExperimentalCycle 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.
Receives: Drug: NKTR-214; Drug: anti-PD-1 therapy; Radiation: Palliative Radiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (10)

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

    Toxicities ≥ Grade 3 is defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Toxicities not "unrelated" to treatment, will be considered treatment-related. Adverse events are evaluated by the physician graded from 1-5 where 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, and 5 = death.

    Measured: up to 14 months (study terminated early)

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

    Toxicities ≥ Grade 3 is defined by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Toxicities not "unrelated" to treatment, will be considered treatment-related. Adverse events are evaluated by the physician and graded from 1-5 where 1 = mild, 2 = moderate, 3 = severe, 4 = life threatening, and 5 = death.

    Measured: up to 14 months (study terminated early)

  3. Progression Free Survival (PFS)

    PFS is the average length of time after the start of treatment in which a person is alive, and their cancer does not grow or spread. PFS is defined as the time from day 1 of treatment until the criteria for disease progression is met as defined by RECIST1.1 or death as a result of any cause.

    Measured: up to 14 months (study terminated early)

  4. Overall Survival (OS)

    OS is defined as time from day 1 of treatment until death as a result of any cause.

    Measured: up to 14 months (study terminated early)

  5. Number of Participants With Clinical Benefit (CB)

    CB will include confirmed complete response (CR) + confirmed partial response (PR) + stable disease at ≥ 6 months (SD) and will be determined as per RECIST1.1.

    Measured: up to 14 months (study terminated early)

  6. Duration of Response

    Duration of response is the period measured from the time that measurement criteria are met for complete or partial response (whichever status is recorded first) until the date that recurrent or progressive disease is objectively documented.

    Measured: up to 14 months (study terminated early)

  7. Health Related Quality of Life as Measured by EORTC QLQ-C30: Global and Functional Sub-Scores

    European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is a measure of health-related quality of life for cancer patients participating in clinical trials. It scores the following domains from 0-100 where higher global or functional scores indicate increased quality of life and higher symptom scores indicate increased symptoms: Global health status (QL2), Physical functioning (PF2), Role functioning (RF2), Emotional functioning (EF), Cognitive functioning (CF), and Social functioning (SF).

    Measured: Baseline at screening, cycle (C)1 day (D)8 (about 2 weeks on study), C2D8 (about 5 weeks on study), C3D8 (about 8 weeks on study), 30-day post (about 12 weeks on study)

  8. Health Related Quality of Life as Measured by EORTC QLQ-C30: Symptom Sub-Scores

    European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is a measure of health-related quality of life for cancer patients participating in clinical trials. It scores the following domains from 0-100 where higher symptom scores indicate increased symptoms: Fatigue (FA), Nausea and vomiting (NV), Pain (PA), Dyspnea (DY), Insomnia (SL), Appetite loss (AP), Constipation (CO), Diarrhea (DI), Financial difficulties (FI)

    Measured: Baseline at screening, cycle (C)1 day (D)8 (about 2 weeks on study), C2D8 (about 5 weeks on study), C3D8 (about 8 weeks on study), 30-day post (about 12 weeks on study)

  9. Health Related Quality of Life as Measured by EORTC QLQ-H&N35 Sub-Scores

    European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire - Head and Neck (EORTC QLQ-H\&N35) is comprised of the following subscales, scored from 0-100 where higher scores indicate increased symptoms: Pain (HNPA), Swallowing (HNSW), Senses problem (HNSE), Speech problems (HNSP), Trouble with social eating (HNSO), Trouble with social contact (HNSC), Less sexuality (HNSX), Teeth (HNTE), Opening mouth (HNOM), Dry mouth (HNDR), Sticky saliva (HNSS), Coughing (HNCO), Felt ill (HNFI), pain killers (HNPK), Nutritional supplements (HNNU), Feeding tube (HNFE), Weight loss (HNFL), Weight gain (HNWG)

    Measured: Baseline at screening, cycle (C)1 day (D)8 (about 2 weeks on study), C2D8 (about 5 weeks on study), C3D8 (about 8 weeks on study), 30-day post (about 12 weeks on study)

  10. Health Related Quality of Life as Measured by EQ-5D Participant Counts

    The EQ-5D is a 5 question measure of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression plus an overall measure of health reported on a visual analog scale. Participant counts are reported for each of 5 dimensions: mobility, self-care, usual activities, pain / discomfort, anxiety / depression.

    Measured: Baseline at screening, cycle (C)1 day (D)8 (about 2 weeks on study), C2D8 (about 5 weeks on study), C3D8 (about 8 weeks on study), 30-day post (about 12 weeks on study)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jun 2021
  2. Study start5 Aug 2021
  3. Primary completion4 Oct 2022
  4. Study completion4 Oct 2022

Why it stopped: study closed by the sponsor

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04936841
Sponsor's protocol ID
UW20092
Other IDs
A533300, SMPH/HUMAN ONCOLOGY, Protocol Version 4/19/2021, 2021-0141
Status last verified
Mar 2024
First submitted
10 Jun 2021
Last updated
4 Apr 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NKTR-214, anti-PD-1 therapy and Palliative Radiation in people with Head and Neck Cancer, run by University of Wisconsin, Madison at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 4 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: up to 7 months (at Standard-of-care imaging 3 to 6 months after Cycle 1)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04936841.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Apr 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in