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A Study of Avelumab in Combination With Axitinib In Non-Small Cell Lung Cancer (NSCLC) or Urothelial Cancer (Javelin Medley VEGF)

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ClinicalTrials.gov Identifier: NCT03472560
Recruitment Status : Active, not recruiting
First Posted : March 21, 2018
Last Update Posted : July 29, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
This is a Phase 2 study to evaluate the safety and efficacy of avelumab in combination with axitinib in patients with advanced or metastatic non-small cell lung cancer (NSCLC) who have received at least one prior platinum containing therapy, and in treatment naïve patients with advanced or metastatic urothelial cancer, who are ineligible for cisplatin containing chemotherapy for their advanced disease.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Urothelial Cancer Drug: Avelumab (MSB0010718C) Drug: Axitinib (AG-013736) Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE 2, OPEN LABEL STUDY TO EVALUATE SAFETY AND CLINICAL ACTIVITY OF AVELUMAB (BAVENCIO (REGISTERED)) IN COMBINATION WITH AXITINIB (INLYTA (REGISTERED)) IN PATIENTS WITH ADVANCED OR METASTATIC PREVIOUSLY TREATED NON-SMALL CELL LUNG CANCER OR TREATMENT NAÏVE CISPLATIN-INELIGIBLE UROTHELIAL CANCER JAVELIN MEDLEY VEGF
Actual Study Start Date : May 2, 2018
Estimated Primary Completion Date : September 18, 2020
Estimated Study Completion Date : September 18, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Avelumab in combination with axitinib
Avelumab administered at 800 mg IV every two weeks in combination with axitinib, 5 mg PO BID.
Drug: Avelumab (MSB0010718C)
IV treatment: Avelumab administered at 800 mg IV every two weeks
Other Name: Bavencio

Drug: Axitinib (AG-013736)
Oral treatment: Axitinib given 5 mg PO BID
Other Name: Inlyta




Primary Outcome Measures :
  1. Confirmed objective response [ Time Frame: Baseline up to approximately 18 months ]
    Objective response (OR) is defined as a confirmed complete response (CR) or partial (PR) per RECIST v 1.1


Secondary Outcome Measures :
  1. Time to Tumor Response (TTR) [ Time Frame: Baseline up to approximately 18 months ]
    Time to Tumor Response (TTR) is defined as the time from the date of first dose of study treatment to the first documentation of objective response [complete response (CR) or partial response (PR)].

  2. Tumor tissue biomarker status (ie, positive or negative based on, for example, PD L1 expression and/or quantitation of tumor mutational burden as well as characterization of the immune repertoire in peripheral blood and/or tumor) [ Time Frame: Screening and optional tumor biopsies obtained upon disease progression. Baseline up to approximately 18 months. ]
    Archived tumor tissue samples and de novo biopsies of primary and/or metastatic lesions. Tumor tissue biomarker status (ie, positive or negative based on, for example, PD L1 expression and/or quantitation of tumor mutational burden as well as characterization of the immune repertoire in peripheral blood and/or tumor).

  3. Anti-drug antibody (ADA) titers against avelumab [ Time Frame: Pre dose on Cycle 1 Day 1 and Day 15, Cycle 2 Day 1, and Day 15 of Cycles 3, 6, 9 and 12 (each cycle is 28 days) ]
    Immunogenicity assessment of avelumab.

  4. Duration of Response (DR) [ Time Frame: Baseline up to approximately 18 months ]
    Duration of Response (DR), is defined as the time from the first documentation of objective response [complete response (CR) or partial response (PR)] to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurs first.

  5. Progression Free Survival (PFS) [ Time Frame: Baseline up to approximately 18 months ]
    Progression Free Survival (PFS) is defined as the time from the date of first dose of study treatment to the date of the first documentation of progressive disease (PD) or death due to any cause, whichever occurs first.

  6. Maximum Observed Plasma Concentration (Cmax) of axitinib [ Time Frame: 2-4 hours post dose Cycle 1 Day 15 and Cycle 2 Day 1 and Day 15 (each cycle is 28 days) ]
    Cmax defined as the maximum plasma concentration of axitinib

  7. Predose Concentration (Ctrough) of avelumab [ Time Frame: Pre dose Cycle 1 Day 1 and Day 15, Cycle 2 Day 1 and Day 15 of Cycles 3, 6, 9, and 12 (each cycle is 28 days) ]
    Ctrough is defined as the concentration at the end of avelumab dosage interval

  8. Predose concentration (Ctrough) of axitinib [ Time Frame: Pre dose Cycle 1 Day 15 and Cycle 2 Day 1 and Day 15 (each cycle is 28 days) take up to 2 hr prior to the start of infusion. ]
    Ctrough is defined as the concentration at the end of axitinib dosage interval

  9. Neutralizing antibodies (nAb) against avelumab [ Time Frame: Pre dose on Cycle 1 Day 1 and Day 15, Cycle 2 Day 1, and Day 15 of Cycles 3, 6, 9 and 12 (each cycle is 28 days) ]
    Immunogenicity assessment of avelumab.

  10. Maximum Observed Plasma Concentration (Cmax) of avelumab [ Time Frame: Post dose Cycle 1 Day 1 and Day 15, Cycle 2 Day 1 (each cycle is 28 days) ]
    Cmax defined as the maximum plasma concentration of avelumab

  11. Overall Survival (OS) [ Time Frame: Baseline up to approximately 18 months ]
    Overall Survival (OS) is defined as the time from the date of first dose of study treatment to the date of death due to any cause.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Non-small cell lung cancer (NSCLC) Cohort: Histologically or cytologically confirmed diagnosis of NSCLC that is locally advanced or metastatic; No activating EGFR mutations, ALK or ROS1 translocations/rearrangements where testing is standard of care; received at least 1 prior platinum‑based chemotherapy regimen for locally advanced or metastatic NSCLC; No more than 2 prior lines of systemic therapy for locally advanced or metastatic disease (If disease progression occurred during or within 6 months after neoadjuvant/adjuvant chemotherapy or radiotherapy‑chemotherapy, the regimen is counted as 1 prior treatment regimen towards the allowed limit of prior treatment regimens); Checkpoint inhibitor naïve.
  • Urothelial Cancer (UC) Cohort: Histologically or cytologically confirmed diagnosis of transitional cell carcinoma (TCC) of the urothelium (if mixed, more than 50% TCC component) including bladder, urethra, ureters, or renal pelvis that is locally advanced or metastatic; No prior systemic treatment for locally advanced or metastatic disease; Prior neoadjuvant or adjuvant therapy is permitted if disease progression occurred >12 months after the completion of therapy; Checkpoint inhibitor naïve; Ineligible for receiving cisplatin‑containing front‑line chemotherapy based at least one of the following criteria: ECOG performance status (PS) 2; Renal dysfunction (defined as creatinine‑clearance <60 ml/min); Grade 2 peripheral neuropathy; Grade 2 hearing loss (hearing loss measured by audiometry of 25 decibels at two contiguous frequencies).
  • At least 1 measurable lesion by RECIST v1.1 not previously irradiated.
  • Availability of an archival FFPE tumor tissue block from primary diagnosis specimen or metastatic specimen or 15 unstained slides (10 minimum). If an archived sample is not available, a fresh tumor biopsy must be performed.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. For UC patients, ECOG performance 2 is permitted (cisplatin ineligibility criterion)

Exclusion Criteria:

  • Prior immunotherapy with an anti‑PD‑1, anti‑PD‑L1, anti‑PD‑L2, anti‑CD137, anti‑OX‑40, anti‑GITR, anti‑LAG‑3, anti‑TIM‑3 or anti‑CTLA‑4 antibody (including ipilimumab).
  • Newly diagnosed brain metastases or known symptomatic brain metastases requiring steroids.
  • Radiologically documented evidence of major blood vessel invasion or encasement by cancer or intratumor cavitation, regardless of tumor histology.
  • Active autoimmune disease (that might deteriorate when receiving an immunostimulatory agent).
  • Current use of immunosuppressive medication (except for those listed in protocol).
  • Known prior severe hypersensitivity to the investigational products /monoclonal antibodies.
  • Known history of immune‑mediated colitis, inflammatory bowel disease, immune‑mediated pneumonitis, pulmonary fibrosis.
  • NCI CTCAE Grade 3 hemorrhage within 28 days prior to study enrollment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03472560


  Show 38 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03472560     History of Changes
Other Study ID Numbers: B9991027
2017-004345-24 ( EudraCT Number )
AVE/ AXI COMBO UC ( Other Identifier: Alias Study Number )
AVE/AXI COMBO UC/NSCLC ( Other Identifier: Alias Study Number )
First Posted: March 21, 2018    Key Record Dates
Last Update Posted: July 29, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Cancer
non-small cell lung cancer
non small cell lung cancer
NSCLC
lung cancer
urothelial cancer
bladder cancer
Avelumab
Bavencio
Axitinib
Inlyta
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Axitinib
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action