A Study Of Avelumab In Combination With Axitinib In Advanced Renal Cell Cancer (JAVELIN Renal 100)

NCT02493751 | Completed Phase 1 Results

• 3 other identifiers: B99910022015-001137-25Javelin Renal 100
• Study Type: interventional
• Target: 55
• Locations: 3 countries
• Sites: 21

Brief Summary

This is a Phase 1b, open-label, multi-center, multiple-dose trial designed to estimate the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D) of avelumab (MSB0010718C) in combination with axitinib (AG-013736). Once the MTD of avelumab administered in combination with axitinib is estimated (dose finding portion), the dose expansion phase will be opened to further characterize the combination in term of safety profile, anti tumor activity, pharmacokinetics, pharmacodynamics and biomarker modulation.

Conditions

Renal Cell Cancer

Keywords

Cancer, renal cell cancer, kidney disease, kidney neoplasms, axitinib

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT: greater than or equal to (\>=) Grade 3 hematologic/non-hematologic toxicity, Grade 3-4 liver-related laboratory test elevation (alanine aminotransferase, aspartate aminotransferase) with Grade 2 elevation of total bilirubin, non-hematologic Grade 3 laboratory abnormality (required medical intervention to treat participant/led to hospitalization), inability to complete \>=75% of first 2 cycles doses of axitinib (from Cycle 1 Day 1 after completion of lead-in period) or 2 infusions of avelumab within DLT observation period due to investigational product related toxicity.

  DLT observation period (from the beginning of Cycle 1 up to the end of Cycle 2 [28 days])

Secondary Outcomes (21)

• Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs)

  Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks)

• Number of Participants With Treatment-related TEAEs

  Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks)

• Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology

  Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks)

• Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry

  Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks)

• Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure

  Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD)

Study Arms (1)

Dose finding phase and dose expansion phase.

EXPERIMENTAL

To test the maximum tolerated dose of avelumab (MSB0010718C) in combination with axitinib (AG-013736)

Drug: Avelumab (MSB0010718C); Drug: Axitinib (AG-013736)

Interventions

Avelumab (MSB0010718C) DRUG

Avelumab with two dose levels: 10 mg/kg IV and 5 mg/kg IV every two weeks to find the maximum tolerated dose in combination with axitinib and continue treatment in a dose expansion.

Dose finding phase and dose expansion phase.

Axitinib (AG-013736) DRUG

Axitinib with two dose levels: 5 mg and 3 mg oral BID to find the maximum tolerated dose in combination with avelumab and continue treatment in a dose expansion.

Dose finding phase and dose expansion phase.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed advanced RCC with clear cell component
• Primary tumor resected
• Availability of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block from a de novo tumor biopsy during screening (biopsied tumor lesion should not be a RECIST target lesion). Alternatively, a recently obtained archival FFPE tumor tissue block (not cut slides) from a primary or metastatic tumor resection or biopsy can be provided if the following criteria are met: 1) the biopsy or resection was performed within 1 year of enrollment AND 2) the patient has not received any intervening systemic anti-cancer treatment from the time the tissue was obtained and enrollment onto the current study. If an FFPE tissue block cannot be provided as per documented regulations,, 15 unstained slides (10 minimum) will be acceptable.
• Availability of an archival FFPE tumor tissue block from primary diagnosis specimen (if available and not provided per above). If an FFPE tissue block cannot be provided, 15 unstained slides (10 minimum) will be acceptable
• At least one measureable lesion as defined by RECIST version 1.1 that has not been previously irradiated.
• Age ≥18 years (≥ 20 years in Japan).
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate bone marrow function, renal and liver functions

You may not qualify if:

• Prior systemic therapy directed at advanced RCC.
• Prior adjuvant or neoadjuvant therapy for RCC if disease progression or relapse has occurred during or within 12 months after the last dose of treatment
• Prior immunotherapy with IL-2, IFN-α, or anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways
• Prior therapy with axitinib as well as any prior therapies with other VEGF pathway inhibitors.
• Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis.
• Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis or symptomatic pulmonary embolism.
• Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (21)

Scottsdale Healthcare Hospitals d/b/a HonorHealth

Scottsdale, Arizona, 85258, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Laura & Isaac Perlmutter Cancer Center At NYU Langone

New York, New York, 10016, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Henry Joyce Cancer Clinic

Nashville, Tennessee, 37232-5310, United States

Location

University of Utah, Huntsman Cancer Hospital

Salt Lake City, Utah, 84112, United States

Location

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Niigata University Medical & Dental Hospital

Chuo-ku, Niigata, Niigata, 951-8520, Japan

Location

Kindai University Hospital

Sayama, Osaka, 589-8511, Japan

Location

Keio University Hospital

Shinjuku-ku, Tokyo, 160-8582, Japan

Location

Mount Vernon Cancer Center, East and North Herts. NHS Trust

London, Middlesex, HA6 2RN, United Kingdom

Location

St Helier Hospital

Carshalton, Surrey, SM5 1AA, United Kingdom

Location

St. Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (5)

• Rini BI, Atkins MB, Choueiri TK, Teresi RE, Rosbrook B, Thakur M, Hutson TE. Plain language summary looking at how long side effects last after treatment with axitinib is stopped in people with advanced renal cell carcinoma. Future Oncol. 2023 Dec;19(40):2623-2629. doi: 10.2217/fon-2023-0233. Epub 2023 Aug 1.

  PMID: 37526095 DERIVED

• Larkin J, Oya M, Martignoni M, Thistlethwaite F, Nathan P, Ornstein MC, Powles T, Beckermann KE, Balar AV, McDermott D, Gupta S, Philips GK, Gordon MS, Uemura H, Tomita Y, Wang J, Michelon E, di Pietro A, Choueiri TK. Avelumab Plus Axitinib as First-Line Therapy for Advanced Renal Cell Carcinoma: Long-Term Results from the JAVELIN Renal 100 Phase Ib Trial. Oncologist. 2023 Apr 6;28(4):333-340. doi: 10.1093/oncolo/oyac243.

  PMID: 36576173 DERIVED

• Masters JC, Khandelwal A, di Pietro A, Dai H, Brar S. Model-informed drug development supporting the approval of the avelumab flat-dose regimen in patients with advanced renal cell carcinoma. CPT Pharmacometrics Syst Pharmacol. 2022 Apr;11(4):458-468. doi: 10.1002/psp4.12771. Epub 2022 Feb 27.

  PMID: 35166465 DERIVED

• Rini BI, Atkins MB, Choueiri TK, Thomaidou D, Rosbrook B, Thakur M, Hutson TE. Time to Resolution of Axitinib-Related Adverse Events After Treatment Interruption in Patients With Advanced Renal Cell Carcinoma. Clin Genitourin Cancer. 2021 Oct;19(5):e306-e312. doi: 10.1016/j.clgc.2021.03.019. Epub 2021 Apr 5.

  PMID: 33947608 DERIVED

• Choueiri TK, Larkin J, Oya M, Thistlethwaite F, Martignoni M, Nathan P, Powles T, McDermott D, Robbins PB, Chism DD, Cho D, Atkins MB, Gordon MS, Gupta S, Uemura H, Tomita Y, Compagnoni A, Fowst C, di Pietro A, Rini BI. Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial. Lancet Oncol. 2018 Apr;19(4):451-460. doi: 10.1016/S1470-2045(18)30107-4. Epub 2018 Mar 9.

  PMID: 29530667 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasms; Kidney Diseases; Kidney Neoplasms

Interventions

avelumab; Axitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2015
• First Posted: July 9, 2015
• Study Start: October 26, 2015
• Primary Completion: April 3, 2018
• Study Completion: March 4, 2021
• Last Updated: February 18, 2022
• Results First Posted: June 21, 2019

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6); US (12); JP (3)