Phase II Randomized Double Blind Trial of PF-04518600, an OX40 Antibody, in Combination With Axitinib Versus Axitinib in Immune-Checkpoint Inhibitor Exposed Patients With Metastatic Renal Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Anti-OX40 Antibody PF-04518600
- Conditions
- Clear Cell Renal Cell Carcinoma
- Sponsor
- University of Southern California
- Enrollment
- 62
- Locations
- 10
- Primary Endpoint
- Progression-free survival (PFS)
- Status
- Active, not recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This randomized phase II trial studies how well axitinib with or without anti-OX40 antibody PF-04518600 work in treating patients with kidney cancer that has spread to other parts of the body. Biological therapies, such as anti-OX40 antibody PF-04518600, use substances made from living organisms that may may stimulate the immune system in different ways and stop tumor cells from growing. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving axitinib with or without anti-OX40 antibody PF-04518600 may work better in treating patients with kidney cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To determine whether a statistically significant improvement in progression free survival exists for patients receiving the combination. SECONDARY OBJECTIVES: I. To determine whether the combination is safe and whether objective response rate (ORR), duration of response (DOR) and overall survival (OS) improve as a result of treatment with combination of axitinib + anti-OX40 antibody PF-04518600 (PF-04518600 \[OX40 Ab\]) compared to axitinib + placebo. TERTIARY OBJECTIVES: I. To determine whether pre and post treatment specimens collected during the trial demonstrate significant changes in tumor microenvironment and enhanced immune response to tumor cells. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive axitinib orally (PO) twice daily (BID) on days 1-14 and anti-OX40 antibody PF-04518600 intravenously (IV) over 60 minutes on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive axitinib as in Arm I and placebo IV on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30, 90, and 180 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing and able to provide informed consent
- •Histological confirmation of renal cell carcinoma (RCC) with a predominantly (\> 50%) clear cell component
- •Metastatic RCC
- •Must have had a nephrectomy (radical or partial) and must provide the cell block from the nephrectomy
- •Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)1.1 criteria
- •Must have progression of disease within 6 months of study enrollment after treatment with only one of the following:
- •Two prior lines of therapy: a VEGF inhibitor (other than axitinib), followed by a single agent PD-1/PDL-1 antibody, or
- •One prior line of therapy: combination of a VEGF inhibitor (other than axitinib) AND a PD1/PDL1 antibody, or
- •Additional prior systemic treatments not allowed
- •Must agree to a fresh core or excisional biopsy from a metastatic site within a 12-week window prior to enrollment; if such a biopsy is already available, cell blocks must be provided; (Note: fine needle aspiration \[FNA\] and bone metastases samples are not acceptable for submission); specimens from the nephrectomy and fresh biopsy must be received and assessed for adequacy of tissue by the Data Coordinating Center (DCC) (University of Southern California \[USC\]) prior to randomization
Exclusion Criteria
- •Patients with known symptomatic brain metastases requiring systemic corticosteroids; patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable; mild neurological deficit is allowed, if it does not interfere with the ability to judge the safety on the trial
- •Prior treatment with an mTOR inhibitor (including, but not limited to, everolimus, temsirolimus, sirolimus, and ridaforolimus)
- •Prior treatment with axitinib
- •History of or active autoimmune disorders (including but not limited to: Crohn's disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Grave's disease) and other conditions that compromise or impair the immune system
- •Active bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) -related illness
- •Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose of study drug; inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease
- •Uncontrolled adrenal insufficiency
- •Any known active chronic liver disease
- •Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast
- •Known medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
Arms & Interventions
Arm I (axitinib, anti-OX40 antibody PF-04518600)
Patients receive axitinib PO BID on days 1-14 and anti-OX40 antibody PF-04518600 IV over 60 minutes on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Intervention: Anti-OX40 Antibody PF-04518600
Arm I (axitinib, anti-OX40 antibody PF-04518600)
Patients receive axitinib PO BID on days 1-14 and anti-OX40 antibody PF-04518600 IV over 60 minutes on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Intervention: Axitinib
Arm I (axitinib, anti-OX40 antibody PF-04518600)
Patients receive axitinib PO BID on days 1-14 and anti-OX40 antibody PF-04518600 IV over 60 minutes on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm II (axitinib, placebo)
Patients receive axitinib as in Arm I and placebo IV on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Intervention: Axitinib
Arm II (axitinib, placebo)
Patients receive axitinib as in Arm I and placebo IV on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm II (axitinib, placebo)
Patients receive axitinib as in Arm I and placebo IV on day 1 beginning with course 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Intervention: Placebo
Outcomes
Primary Outcomes
Progression-free survival (PFS)
Time Frame: Time from randomization until the earliest of documented disease progression (confirmed progression of disease) or death, assessed for up to 180 days
The statistical comparison of PFS in the two treatment arms will be based on the stratified logrank test.
Secondary Outcomes
- Incidence of unacceptable toxicity(Up to the beginning of the third course (29 days))
- ORR defined as either complete response or partial response occurring any time during treatment and assessed by RECIST 1.1 and immune-related RECIST (irRECIST) criteria(Up to 180 days)