Bempegaldesleukin (NKTR-214) With Radiation and Anti-PD-1 Immunotherapy for Head and Neck Squamous Cell Carcinoma
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|ClinicalTrials.gov Identifier: NCT04936841|
Recruitment Status : Recruiting
First Posted : June 23, 2021
Last Update Posted : August 26, 2021
|Condition or disease||Intervention/treatment||Phase|
|Head and Neck Cancer||Drug: NKTR-214 Drug: anti-PD-1 therapy Radiation: Palliative Radiation||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||August 5, 2021|
|Estimated Primary Completion Date :||June 2024|
|Estimated Study Completion Date :||June 2026|
Experimental: NKTR-214, anti-PD therapy plus Palliative Radiation
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.
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)
Other Name: bempegaldesleukin
Drug: anti-PD-1 therapy
immunotherapy drug, monoclonal antibody
Other Name: Pembrolizumab
Radiation: Palliative Radiation
radiation to relieve symptoms
- Objective Response Rate (ORR) [ Time Frame: up to 7 months (at Standard-of-care imaging 3 to 6 months after Cycle 1) ]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.
- Adverse Events Greater than or equal to Grade 3 [ Time Frame: up to 5 years ]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.
- Progression Free Survival (PFS) [ Time Frame: up to 5 years ]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.
- Overall Survival (OS) [ Time Frame: up to 5 years ]OS is defined as time from day 1 of treatment until death as a result of any cause.
- Clinical Benefit (CB) [ Time Frame: up to 5 years ]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.
- Duration of Response [ Time Frame: up to 5 years ]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.
- Health Related Quality of Life as measured by EORTC QLQ-C30 Score [ Time Frame: up to 5 years ]European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is a 30 item instrument with a total possible range of scores 30 - 126, where lower scores indicate improved quality of life.
- Health Related Quality of Life as measured by EORTC QLQ-H&N35 Score [ Time Frame: up to 5 years ]European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire - Head and Neck (EORTC QLQ-H&N35) is a 35 item instrument where 30 items are scored 1 (not at all) 2 (a little) 3 (quite a bit) and 4 (very much), and 5 items are scored 1 (no) and 2 (yes), for a total possible range of scores between 35 - 130 where lower scores indicate better health related quality of life.
- Health Related Quality of Life as measured by EQ-5D Score [ Time Frame: up to 5 years ]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. Scores are normalized between 1 (full health) and 0 (dead).
- Expression of PD-L1 by histology [ Time Frame: up to 3 months ]PD-L1 expression has been shown to predict response to immunotherapy regimens. If PD-L1 expression correlates with outcome, it could be used in the future to select patients who have greatest benefit from this regimen.
- Levels of IFN-γ expressing and CD122+ T cells in Peripheral Blood Mononuclear Cells (PBMC) [ Time Frame: up to 5 years ]Evaluation of the in vivo immune response will help better define the mechanism of action of this combination therapy.
- Diversity and clonality of the T cell receptor repertoire by deep sequencing of PBMC [ Time Frame: up to 5 years ]Evaluation of the in vivo immune response will help better define the mechanism of action of this combination therapy.
- Levels of tumor infiltrating lymphocytes by histology [ Time Frame: up to 3 months ]Evaluation of the in vivo immune response will help better define the mechanism of action of this combination therapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04936841
|Contact: Cancer Connectfirstname.lastname@example.org|
|United States, Wisconsin|
|University of Wisconsin||Recruiting|
|Madison, Wisconsin, United States, 53792|
|Contact: Cancer Connect 800-622-8922 email@example.com|
|Study Chair:||Zachary Morris, MD, PhD||University of Wisconsin, Madison|
|Study Chair:||Paul Harari, MD||University of Wisconsin, Madison|
|Principal Investigator:||Adam Burr, MD, PhD||University of Wisconsin, Madison|
|Principal Investigator:||Justine Bruce, MD||University of Wisconsin, Madison|