Nivolumab Plus Axitinib in Patients With Anti-PD1 Refract... | NCT04493203

NCT04493203

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Sponsor/Collaborators Module

Name	Class
Pfizer	INDUSTRY
Bristol-Myers Squibb	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Nivolumab plus Axitinib	Experimental	Nivolumab 480mg, IV, every 4 weeks, for up to two years. Axitinib 5mg, PO, BID, for up to two years.	Drug: Nivolumab Drug: Axitinib

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Nivolumab	Drug	Nivolumab is a human IgG4 monoclonal antibody that blocks PD-1. It is a type of Immunotherapy and works as a checkpoint inhibitor, blocking a signal that prevents activation of T cells from attacking the cancer.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Response Rate (ORR)	Percentage of patients who achieve Complete Response (CR) or Partial Response (PR) as best response by RECIST v1.1 criteria (with exact 95% CI). Per RECIST v1.1, Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.	Up to 12 weeks from baseline (after treatment)
Overall Response Rate (ORR) - Prior Ipilimumab / Nivolumab Treatment	Percentage of patients (prior Ipilimumab/Nivolumab treatment) who achieve Complete Response (CR) or Partial Response (PR) as best response by RECIST v1.1 criteria (with exact 95% CI). Per RECIST v1.1, Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.	Up to 12 weeks from baseline (after treatment)
Overall Response Rate (ORR) - no Prior Ipilimumab / Nivolumab	Percentage of patients (no prior Ipilimumab/Nivolumab treatment) who achieve Complete Response (CR) or Partial Response (PR) as best response by RECIST v1.1 criteria (with exact 95% CI). Per RECIST v1.1, Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.	Up to 12 weeks from baseline (after treatment)
Overall Response Rate (ORR) - Prior Lines of Therapy <=3	Percentage of patients (<=3 prior lines of therapy) who achieve Complete Response (CR) or Partial Response (PR) as best response by RECIST v1.1 criteria (with exact 95% CI). Per RECIST v1.1, Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

Secondary Outcomes

Measure	Description	Time Frame
Overall Survival (OS) - Overall Cohort	The median number of months from the start of treatment that patients remain alive, until death from any cause.	Up to 45 months
6-month Overall Survival (OS)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have unresectable (stage III) or advanced (stage IV) cutaneous or mucosal melanoma. Patients with uveal melanoma are not eligible.
Progressed on prior anti-PD1 therapy with or without anti-CTLA4 therapy. Patients may have progressed in the adjuvant setting if treated within the last 6 months. Prior treatment with BRAF/MEK inhibitors permitted, however, not required. Progression must be radiographic, and progression of disease will be confirmed by a radiologist. Patients must have progressed during anti-PD-1 therapy, defined as unequivocal progression on or within 3 months of the last dose of anti-PD-1 therapy if treated in the metastatic setting, or within 6 months if treated in the adjuvant setting.
Have measurable disease based on RECIST 1.1.
Patients do not have to have biopsiable disease to be eligible. However, patients with biopsiable disease must undergo biopsy at study entry and at week 12.
Have a performance status of 0 or 1 on the ECOG Performance Scale.
Demonstrate adequate organ function, per protocol
Patients with brain metastases are permitted if they are asymptomatic or previously treated with CNS directed therapy with stable CNS disease for at least 2 weeks. Stable is defined as asymptomatic or not progressing on imaging.
Female patients of childbearing potential - negative pregnancy testing; use of birth control, surgically sterile or abstain from heterosexual activity during study and for 5 months after the last dose of study medication.
Male subjects - agree to use an adequate contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy; abstinence acceptable

Exclusion Criteria:

Prior history of Grade 3 or 4 immune-related adverse events or immune-related adverse events requiring discontinuation of prior therapies.
History of hypertensive crisis or hypertensive encephalopathy.
Significant thrombotic (e.g. deep vein thrombosis or pulmonary embolism) or hemorrhagic event within 6 months prior to enrollment.
History of prior immune-related adverse event due to an anti-PD1 or anti-CTLA4 that has not resolved to grade 1 on a steroid dose of prednisone 10 mg or less at the time of study entry (excluding vitiligo and endocrine toxicity).
Patients with prior myocarditis or other immune-mediated cardiac adverse events, prior Guillain-Barre syndrome, encephalitis, meningitis, or transverse myelitis, prior Stevens-Johnson syndrome or toxic epidermal necrolysis are excluded regardless of grade.
Poorly controlled hypertension defined as systolic blood pressure (SBP) > 160 and/or diastolic blood pressure (DBP) > 100 despite antihypertensives. If subject is above this goal, treatment with anti-hypertensives to achieve better blood pressure control is permitted. Ambulatory blood pressure assessment is permitted if there is concern for discrepant blood pressure readings while patients are in clinic.
Has Class III or IV heart failure based on the New York Heart Association.
Has had major surgery within 4 weeks of randomization. This does not include outpatient surgeries that do not require post-operative admission.
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (greater than the equivalent of prednisone 10 mg daily, unless for prior endocrine toxicity) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (premedication with steroids for contrast imaging studies is permitted).
Has a known history of active TB (Bacillus Tuberculosis).
Hypersensitivity to nivolumab or axitinib, or any of their excipients.
Has had prior chemotherapy or targeted small molecule therapy within 1 week prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
Has had radiation within 2 weeks of randomization.
Has current use or anticipated need for treatment with drugs or foods that are known strong cytochrome P450 (CYP34A4/5) inhibitors including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice. NOTE: The topical use of these medications, such as 2% ketoconazole cream is allowed.
Has current use or anticipated need for treatment with drugs known to be strong CYP3A4/5 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort.
Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy, in situ cervical cancer, in situ colon cancer, or nonmetastatic prostate cancer not on systemic therapy.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 2 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
Has an active infection requiring systemic IV antibiotic therapy.
Has had any of the following within the past 6 months
Myocardial infarction or unstable angina
Ventricular arrythmia
Acute decompensated heart failure
Cerebrovascular accident
Hypertensive emergency requiring ICU admission
Presence of a disorder that may impact absorption of axitinib, such as inability to take oral medication, requirement for IV alimentation, prior gastric resection, treatment for active peptic ulcer confirmed by endoscopy within the past 3 months, active GI bleed, malabsorption syndrome.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 5 months after the last dose of trial treatment for females and 7 months after the last dose of trial treatment for males.
Has a known history of HIV (HIV 1/2 antibodies) if the CD4 count is less than 350 mm3 or serum HIV viral load is < 25,000 IU/mL.
Has a known history of or is positive for hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (hepatitis C virus [HCV] RNA [qualitative] is detected). Note: Without known history, testing only needs to be performed if there is clinical suspicion for Hepatitis B or C.
Is currently incarcerated or otherwise detained.
Has received a live vaccine within 30 days of planned start of study therapy. (intranasal iNinfluenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed)

Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.

Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

Contacts/Locations Module

Name	Affiliation	Role
Yana Najjar, MD	UPMC Hillman Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
UPMC Hillman Cancer Center		Pittsburgh	Pennsylvania	15232	United States

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

ID	Title	Description
FG000	Nivolumab Plus Axitinib	Nivolumab 480mg, IV, every 4 weeks, for up to two years. Axitinib 5mg, PO, BID, for up to two years.

Baseline Characteristics Module

ID	Title	Description
BG000	Nivolumab Plus Axitinib	Nivolumab 480mg, IV, every 4 weeks, for up to two years. Axitinib 5mg, PO, BID, for up to two years.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Response Rate (ORR)

Percentage of patients who achieve Complete Response (CR) or Partial Response (PR) as best response by RECIST v1.1 criteria (with exact 95% CI). Per RECIST v1.1, Complete Response (CR) is defined as disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. Partial Response (PR) is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

Treated patients who were evaluable for radiologic response.

Posted

Number

95% Confidence Interval

percentage of patients

Up to 12 weeks from baseline (after treatment)

ID	Title	Description
OG000	Nivolumab Plus Axitinib	Nivolumab 480mg, IV, every 4 weeks, for up to two years. Axitinib 5mg, PO, BID, for up to two years.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Nivolumab Plus Axitinib	Nivolumab 480mg, IV, every 4 weeks, for up to two years. Axitinib 5mg, PO, BID, for up to two years.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Heart failure	Cardiac disorders	CTCAE (5.0)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE (5.0)	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Barbara Stadterman, MPH, MSCCR, CCRP, Clinical Research Manager	UPMC Hillman Cancer Center	4126475554		stadtermanbm@upmc.edu

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jan 3, 2024	Apr 11, 2025	Prot_SAP_000.pdf

Submission Tracking

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

ID	Term
D000077594	Nivolumab
D000077784	Axitinib

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins

Masking Info

Nivolumab plus Axitinib

Percentage of patients alive from the start of treatment that patients remain alive, until death from any cause up to 6 months.

Units	Counts
Participants	OG00031

EG0001 affected31 at risk

EG00016 affected31 at risk

Title	Measurements
	OG00055

Title	Measurements
	OG00066.7

Title	Measurements
	OG00043.8

Title	Measurements
	OG00028.6

Title	Measurements
	OG00064.7

Title	Measurements
	OG00057.1

Title	Measurements
	OG00050.0

Title	Measurements
	OG00063.6

Title	Measurements
	OG00046.7

Title	Measurements
	OG00062.5

Title	Measurements
	OG0001