Head Neck, Squamous Cell Carcinoma of Head and Neck
Conditions
Brief summary
To learn if magrolimab, along with a combination of commercially-available drugs (cetuximab, pembrolizumab, and docetaxel) can help to control HNSCC in combination with other drugs. The safety of magrolimab will also be studied.
Detailed description
Primary Objectives: -Objective response rate (ORR) per RECIST v1.1 Secondary Objectives: * Adverse events rates per CTCAE V5.0 (appendix) * Duration of response (DOR) * Progression free survival (PFS) per RECIST v1.1 * Overall survival (OS) per RECIST v1.1 Exploratory Objectives: -Assessment of blood and tissue-based biomarkers predictive of response to therapy
Interventions
DRUGPembrolizumab
Given by IV (vein)
DRUGMagrolimab
Given by IV (vein)
DRUGcetuximab
Given by IV (vein)
DRUGDocetaxel
Given by IV (vein)
Sponsors
Gilead Sciences
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All patients must meet all of the following inclusion criteria to be eligible for participation in this study: 1. Patient must have a diagnosis of recurrent or metastatic oropharynx, oral cavity, hypopharynx, or larynx squamous cell carcinoma (HNSCC), not amenable to curative-intent local therapy with known PD-L1 CPS determined by an FDA-approved test. Patients with unknown primary squamous cell carcinoma presumed from the head and neck are also eligible upon discussion with study principal investigator. 2. Patient has provided informed consent. 3. Patient is willing and able to comply with clinic visits and procedures outlined in the study protocol. 4. Male or female ≥ 18 years of age 5. ECOG performance status of 0 or 1 6. Laboratory measurements, blood counts: 1. Hemoglobin ≥ 9 g/dL within 24 hours prior to initial dose of study treatment. Red blood cell transfusions are permitted to meet the hemoglobin inclusion criteria, within limits set per exclusion criterion 6. 2. Absolute neutrophil count ≥ 1.2 x 109/mL 3. Platelets ≥ 100 x 109/mL 7. Laboratory measurements, renal function: Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or if elevated, a calculated glomerular filtration rate \> 40 mL/min/1.73m2 per CKD-EPI equation. 8. Laboratory measurements, hepatic function: 1. AST and ALT ≤ 2.5 x ULN or ≤ 5 x ULN in patients with liver metastases 2. Total bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN and primarily unconjugated if patient has a documented history of Gilbert's syndrome or genetic equivalent 9. Laboratory measurements, coagulation function: 1. International normalized ratio or prothrombin time (PT) ≤ 1.5 x ULN unless patient is receiving anticoagulation therapy, as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use for anticoagulants 2. Activated partial thromboplastin time or PTT ≤ 1.5 x ULN unless patient is receiving anticoagulation therapy, as long as PT or PTT is within therapeutic range of intended use for anticoagulants 10. Female patients with reproductive potential must practice two effective contraceptive measures for the duration of study drug therapy and for at least 6 months after completion of study therapy. The two birth control methods can be either two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. The following are considered adequate barrier methods of contraception: diaphragm, condom, copper intrauterine device, sponge, or spermicide. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents). 11. Male patients who are sexually active with women with reproductive potential must agree to use contraception for the duration of treatment and for at least 6 months after completion of study therapy. 12. Measurable disease according to RECIST, version 1.1 13. Patients must be willing to provide baseline tumor tissue from a core or excisional biopsy (fine needle aspirate is not adequate). A newly obtained biopsy (within 90 days prior to study treatment start) is strongly preferred, but an archival sample is acceptable. 14. Absence of active auto-immune disease or any other contra-indication to pembrolizumab, cetuximab, docetaxel or magrolimab Cohort A: In addition to meeting the inclusion criteria for all patients, patients who are enrolled into Cohort A must fulfill the following cohort-specific inclusion criteria: 15. PD-L1 CPS must be ≥ 1 16. Patients should not have had prior systemic therapy administered in the recurrent or metastatic setting. Systemic therapy that was completed more than 3 months prior to signing consent if given as part of multimodal treatment for locally advanced disease is allowed. 17. Patients could have received anti-PD1 or anti-PD-L1 in the neoadjuvant or adjuvant setting as part of a clinical trial, as long as the patient has not progressed during it and there has been at least a 6 months disease-free interval since last administration of anti-PD1 or anti-PD-L1 in the curative intent setting. Cohort B: In addition to meeting the inclusion criteria for all patients, patients who are enrolled into Cohort B must fulfill the following cohort-specific inclusion criterion: 17\) Patients must have received at least 1 and no more than 2 lines of prior systemic anticancer therapy in the recurrent/metastatic setting not including docetaxel but including anti-PD1. Patients must have progressed on anti-PD1 (radiographically or clinically) or developed intolerable adverse events attributed to anti-PD1 that lead to treatment discontinuation and eventual disease progression. Patients with contra-indications to anti-PD1 are also eligible.
Exclusion criteria
Patients who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 140 days | Objective Response Rate (ORR) per RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v.1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient growth to qualify for PD; Progressive Disease (PD), \>= 20% increase in the sum of the longest diameter with an absolute increase of at least 5 mm or the appearance of new lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | 145 days | Adverse events (AEs) are categorized as follows: Treatment-Emergent Adverse Events (TEAEs), which refer to any AEs that arise or worsen in severity after the initiation of treatment with the study product; and Treatment-Related Adverse Events (TRAEs), defined as TEAEs that are considered possibly, probably, or definitely related to the treatment. Adverse Events were graded 1 to 5 via CTAE 5.0 guidelines. All AEs, whether serious or non-serious, will be captured from the time of the first administration of the investigational agent until 30 days following the last dose of study drug or until the initiation of alternative anticancer therapy |
| Duration of Response (DOR) | 2 weeks and 1 day | Time (the duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. |
| Number of Participants With Progression Free Survival (PFS) and/or Death | 4 months and 4 days | Progression free survival (PFS) per RECIST v1.1. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of the longest diamester of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A Anti-PD1 naïve, treatment with Magrolimab, Cetuximab, and Pembrolizumab and Cohort A Maintenance
Anti-PD1 naïve, magro IV QW/cetux IV QW/pembro IV Q3W | 1 |
| Cohort B Anti-PD1 refractory, treatment with Magrolimab, Cetuximab and Docetaxel
Anti-PD1 refractory magro IV QW/cetux IV QW/docetaxel IV QW | 3 |
| Total | 4 |
Baseline characteristics
| Characteristic | Cohort A | Cohort B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 4 Participants |
| Region of Enrollment United States | 1 participants | 3 participants | 4 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 3 |
| other Total, other adverse events | 1 / 1 | 3 / 3 |
| serious Total, serious adverse events | 0 / 1 | 1 / 3 |
Outcome results
Primary
Objective Response Rate (ORR)
Objective Response Rate (ORR) per RECIST v1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v.1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient growth to qualify for PD; Progressive Disease (PD), \>= 20% increase in the sum of the longest diameter with an absolute increase of at least 5 mm or the appearance of new lesions
Time frame: 140 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A | Objective Response Rate (ORR) | Partial Response (PR) | 1 Participants |
| Cohort A | Objective Response Rate (ORR) | Stable Disease (SD) | 0 Participants |
| Cohort B | Objective Response Rate (ORR) | Partial Response (PR) | 0 Participants |
| Cohort B | Objective Response Rate (ORR) | Stable Disease (SD) | 3 Participants |
Secondary
Duration of Response (DOR)
Time (the duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented.
Time frame: 2 weeks and 1 day
Population: Cohort A - participant withdrew consent after 15 days. Cohort B -- no patients in cohort B achieved a PR.
Secondary
Number of Participants With Progression Free Survival (PFS) and/or Death
Progression free survival (PFS) per RECIST v1.1. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) as a 20% increase in the sum of the longest diamester of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: 4 months and 4 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A | Number of Participants With Progression Free Survival (PFS) and/or Death | Disease progression | 0 Participants |
| Cohort A | Number of Participants With Progression Free Survival (PFS) and/or Death | Death on study | 0 Participants |
| Cohort B | Number of Participants With Progression Free Survival (PFS) and/or Death | Disease progression | 1 Participants |
| Cohort B | Number of Participants With Progression Free Survival (PFS) and/or Death | Death on study | 0 Participants |
Secondary
Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Adverse events (AEs) are categorized as follows: Treatment-Emergent Adverse Events (TEAEs), which refer to any AEs that arise or worsen in severity after the initiation of treatment with the study product; and Treatment-Related Adverse Events (TRAEs), defined as TEAEs that are considered possibly, probably, or definitely related to the treatment. Adverse Events were graded 1 to 5 via CTAE 5.0 guidelines. All AEs, whether serious or non-serious, will be captured from the time of the first administration of the investigational agent until 30 days following the last dose of study drug or until the initiation of alternative anticancer therapy
Time frame: 145 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 3 : Unrelated | 1 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 2 : Unlikely | 0 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 3 : Possible | 0 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 2 : Unrelated | 3 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 2 : Definite | 1 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 1 : Definite | 1 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 3 : Unlikely | 0 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 1 : Possible | 8 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 2 : Possible | 3 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 1 : Probable | 2 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 3 : Probable | 0 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 1 : Unlikely | 3 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 2 : Probable | 0 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 1 : Unrelated | 9 Treatment-Emergent Adverse Events TEAEs |
| Cohort A | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 3 : Definite | 0 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 1 : Unrelated | 5 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 3 : Definite | 1 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 3 : Possible | 2 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 3 : Probable | 0 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 3 : Unlikely | 0 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 3 : Unrelated | 0 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 2 : Definite | 2 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 2 : Possible | 2 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 2 : Probable | 3 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 2 : Unlikely | 0 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 2 : Unrelated | 1 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 1 : Definite | 8 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 1 : Possible | 17 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 1 : Probable | 5 Treatment-Emergent Adverse Events TEAEs |
| Cohort B | Number of Treatment-Emergent Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 | Grade 1 : Unlikely | 10 Treatment-Emergent Adverse Events TEAEs |