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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-Small Cell Lung Cancer, Urothelial Cancer

Intervention / Treatment
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* Drug: Avelumab (MSB0010718C)
* Drug: Axitinib (AG-013736)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avelumab in combination with axitinib<br>Avelumab administered at 800 mg IV every two weeks in combination with axitinib, 5 mg PO BID. | Drug: Avelumab (MSB0010718C)<br>* IV treatment: Avelumab administered at 800 mg IV every two weeks<br>* Other names: Bavencio;Drug: Axitinib (AG-013736)<br>* Oral treatment: Axitinib given 5 mg PO BID<br>* Other names: Inlyta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed objective response | Objective response (OR) is defined as a confirmed complete response (CR) or partial (PR) per RECIST v 1.1 | Baseline up to approximately 42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Tumor Response (TTR) | 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)]. | Baseline up to approximately 42 months | 
| 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) | 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). | Screening and optional tumor biopsies obtained upon disease progression. Baseline up to approximately 42 months. | 
| Anti-drug antibody (ADA) titers against avelumab | Immunogenicity assessment of avelumab. | 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) | 
| Duration of Response (DR) | 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. | Baseline up to approximately 42 months | 
| Progression Free Survival (PFS) | 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. | Baseline up to approximately 42 months | 
| Maximum Observed Plasma Concentration (Cmax) of axitinib | Cmax defined as the maximum plasma concentration of axitinib | 2-4 hours post dose Cycle 1 Day 15 and Cycle 2 Day 1 and Day 15 (each cycle is 28 days) | 
| Predose Concentration (Ctrough) of avelumab | Ctrough is defined as the concentration at the end of avelumab dosage interval | 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) | 
| Predose concentration (Ctrough) of axitinib | Ctrough is defined as the concentration at the end of axitinib dosage interval | 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. | 
| Neutralizing antibodies (nAb) against avelumab | Immunogenicity assessment of avelumab. | 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) | 
| Maximum Observed Plasma Concentration (Cmax) of avelumab | Cmax defined as the maximum plasma concentration of avelumab | Post dose Cycle 1 Day 1 and Day 15, Cycle 2 Day 1 (each cycle is 28 days) | 
| Overall Survival (OS) | 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. | Baseline up to approximately 42 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Axitinib, Inlyta, Cancer, non-small cell lung cancer, non small cell lung cancer, NSCLC, lung cancer, urothelial cancer, bladder cancer, Avelumab, Bavencio