Metastatic Head and Neck Cancer, Recurrent Head and Neck Cancer
Conditions
Keywords
Head and Neck Cancer, Head and Neck Squamous-Cell Carcinoma, HNSCC, BEMPEG, Bempegaldesleukin, NKTR-214, Keytruda, Pembrolizumab, PROPEL-36
Brief summary
This is a multicenter, randomized, open-label, Phase 2/3 study that will evaluate the efficacy and safety of bempegaldesleukin (BEMPEG; NKTR-214) combined with pembrolizumab compared with pembrolizumab monotherapy in patients with recurrent or metastatic HNSCC with positive PD-L1 expression (CPS ≥ 1).
Interventions
Specified dose on specified days
DRUGPembrolizumab
Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual.
Sponsors
SFJ Pharmaceuticals, Inc.
Merck Sharp & Dohme LLC
Nektar Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provide written, informed consent to participate in the study and follow the study procedures. * Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF). * Have histologically or cytologically-confirmed recurrent or metastatic HNSCC that is considered incurable by local therapies. * No prior systemic therapy for recurrent or metastatic disease. * The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. * Patients may not have a primary tumor site of nasopharynx (any histology) and/or unknown primary. * Have measurable disease based on RECIST 1.1 as determined by the local site Investigator. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Measure Description: GRADE - ECOG PERFORMANCE STATUS 0 - Fully active, able to carry on all pre-disease performance without restriction 1 - Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work 2- Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours • The tumor must have positive PD-L1 expression (i.e., CPS ≥1)
Exclusion criteria
* Has disease that is suitable for local therapy administered with curative intent. * Has progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC. * Has had radiation therapy (or other non-systemic therapy) within 2 weeks prior to initiation of study drug * Has a life expectancy of less than 3 months and/or has rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) as determined by the Investigator. * Has a known additional malignancy that is progressing or has required active treatment within 5 years prior to the first dose of study drug * Has an active autoimmune disease that has required systemic treatment in the past 2 years * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy * Use of an investigational agent or an investigational device within 28 days before the first dose of study drug. * Prior treatment with an anti PD-1, anti PD-L1, anti-PD-L2, or anti CTLA-4 antibody, agents that target IL-2 pathway, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Approximately 2 years | — |
| Objective Response Rate | Approximately 2 years | To compare the objective response rate (ORR) of bempegaldesleukin plus pembrolizumab versus pembrolizumab monotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | Approximately 2 years | To compare progression-free survival (PFS) of bempegaldesleukin plus pembrolizumab versus pembrolizumab monotherapy. |
| Time to Deterioration | Approximately 2 years | The time from baseline to a ≥ 10-point decrease with confirmation by the subsequent visit of a ≥ 10-point deterioration from baseline in: • Global health status/quality of life assessment based on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30). The EORTC QLQ-C30 is a 30-item questionnaire designed to assess the quality of life of cancer patients. All scale scores are linearly converted to range from 0 to 100. A higher total score indicates a better level of functioning. • Pain and Swallowing based on respective multi-item scales of EORTC QLQ head and neck cancer specific module (EORTC QLQ-H&N35). EORTC QLQ-H&N35 consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. All scale scores are linearly converted to range from 0 to 100. A higher total score indicates increased severity of symptoms. |
| Change in Global Health Status/Quality of Life | Approximately 2 years | To compare mean change from baseline in global health status/quality of life scale of EORTC QLQ-C30. The EORTC QLQ-C30 is composed of multi-item scales and single item measures. These include 5 functional scales (physical, role, emotional, cognitive, and social), 3 symptom scales (fatigue, nausea/vomiting, and pain), a global health status/HRQoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All scale scores are linearly converted to range from 0 to 100. A higher total score indicates a better level of functioning. |
| Percentage of Patients With Treatment-Emergent Adverse Events and Serious Adverse Events | Screening baseline through end of study, approximately 2 years | Compare the overall safety and tolerability based on assessments of treatment-emergent adverse events and serious adverse events |
Countries
Austria, Greece, Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BEMPEG + Pembrolizumab Bempegaldesleukin plus pembrolizumab every 3 weeks (q3w) for up to 35 cycles (approximately 2 years).
Bempegaldesleukin: Specified dose on specified days
Pembrolizumab: Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual. | 1 |
| Pembrolizumab Monotherapy Pembrolizumab monotherapy q3w for up to 35 cycles (approximately 2 years).
Pembrolizumab: Pembrolizumab (anti-PD-1) will be dosed as per the pharmacy manual. | 0 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Study was terminated in consonance with discontinuation of bempegaldesleukin program. | 1 | 0 |
Baseline characteristics
| Characteristic | Total | BEMPEG + Pembrolizumab |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants |
| Age, Continuous | 69 years | 69 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants |
| Region of Enrollment Austria | 0 participants | 0 participants |
| Region of Enrollment Greece | 0 participants | 0 participants |
| Region of Enrollment Italy | 0 participants | 0 participants |
| Region of Enrollment United States | 1 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 0 |
| other Total, other adverse events | 1 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
Objective Response Rate
To compare the objective response rate (ORR) of bempegaldesleukin plus pembrolizumab versus pembrolizumab monotherapy.
Time frame: Approximately 2 years
Primary
Overall Survival
Time frame: Approximately 2 years
Population: Nektar and BMS Study PIVOT-IO-001 did not meet its primary EP of demonstrating an efficacy advantage from addition of BEMPEG to nivolumab in patients with previously untreated inoperable or metastatic melanoma. PIVOT-09 (RCC) and PIVOT-10 (uroth C) studies also reported negative topline results. Based on these 3 large negative studies, Nektar and SFJ in consultation with the study IDMC made the decision to discontinue this trial. At termination, 1 patient was enrolled and treated for 2 cycles.
Secondary
Change in Global Health Status/Quality of Life
To compare mean change from baseline in global health status/quality of life scale of EORTC QLQ-C30. The EORTC QLQ-C30 is composed of multi-item scales and single item measures. These include 5 functional scales (physical, role, emotional, cognitive, and social), 3 symptom scales (fatigue, nausea/vomiting, and pain), a global health status/HRQoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All scale scores are linearly converted to range from 0 to 100. A higher total score indicates a better level of functioning.
Time frame: Approximately 2 years
Secondary
Percentage of Patients With Treatment-Emergent Adverse Events and Serious Adverse Events
Compare the overall safety and tolerability based on assessments of treatment-emergent adverse events and serious adverse events
Time frame: Screening baseline through end of study, approximately 2 years
Secondary
Progression-Free Survival
To compare progression-free survival (PFS) of bempegaldesleukin plus pembrolizumab versus pembrolizumab monotherapy.
Time frame: Approximately 2 years
Secondary
Time to Deterioration
The time from baseline to a ≥ 10-point decrease with confirmation by the subsequent visit of a ≥ 10-point deterioration from baseline in: • Global health status/quality of life assessment based on the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30). The EORTC QLQ-C30 is a 30-item questionnaire designed to assess the quality of life of cancer patients. All scale scores are linearly converted to range from 0 to 100. A higher total score indicates a better level of functioning. • Pain and Swallowing based on respective multi-item scales of EORTC QLQ head and neck cancer specific module (EORTC QLQ-H&N35). EORTC QLQ-H&N35 consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. All scale scores are linearly converted to range from 0 to 100. A higher total score indicates increased severity of symptoms.
Time frame: Approximately 2 years