Clinical Trials /

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

NCT03472560

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
  • Transitional Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: B9991027
  • SECONDARY ID: 2017-004345-24
  • SECONDARY ID: AVE/ AXI COMBO UC
  • SECONDARY ID: AVE/AXI COMBO UC/NSCLC
  • NCT ID: NCT03472560

Conditions

  • Non-Small Cell Lung Cancer
  • Urothelial Cancer

Interventions

DrugSynonymsArms
Avelumab (MSB0010718C)BavencioAvelumab in combination with axitinib
Axitinib (AG-013736)InlytaAvelumab in combination with axitinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Avelumab in combination with axitinibExperimentalAvelumab administered at 800 mg IV every two weeks in combination with axitinib, 5 mg PO BID.
  • Avelumab (MSB0010718C)
  • Axitinib (AG-013736)

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed objective response
Time Frame:Baseline up to approximately 18 months
Safety Issue:
Description:Objective response (OR) is defined as a confirmed complete response (CR) or partial (PR) per RECIST v 1.1

Secondary Outcome Measures

Measure:Time to Tumor Response (TTR)
Time Frame:Baseline up to approximately 18 months
Safety Issue:
Description: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)].
Measure: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.
Safety Issue:
Description: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).
Measure: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)
Safety Issue:
Description:Immunogenicity assessment of avelumab.
Measure:Duration of Response (DR)
Time Frame:Baseline up to approximately 18 months
Safety Issue:
Description: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.
Measure:Progression Free Survival (PFS)
Time Frame:Baseline up to approximately 18 months
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:Cmax defined as the maximum plasma concentration of axitinib
Measure: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)
Safety Issue:
Description:Ctrough is defined as the concentration at the end of avelumab dosage interval
Measure: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.
Safety Issue:
Description:Ctrough is defined as the concentration at the end of axitinib dosage interval
Measure: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)
Safety Issue:
Description:Immunogenicity assessment of avelumab.
Measure: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)
Safety Issue:
Description:Cmax defined as the maximum plasma concentration of avelumab
Measure:Overall Survival (OS)
Time Frame:Baseline up to approximately 18 months
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • Cancer
  • non-small cell lung cancer
  • non small cell lung cancer
  • NSCLC
  • lung cancer
  • urothelial cancer
  • bladder cancer
  • Avelumab
  • Bavencio
  • Axitinib
  • Inlyta

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