Clinical Trials /

Avelumab in Metastatic or Locally Advanced Solid Tumors (JAVELIN Solid Tumor)

NCT01772004

Description:

This is a Phase 1, open-label, dose-escalation trial of avelumab [antibody targeting programmed death ligand 1 (anti PD-L1)] with consecutive parallel group expansion in subjects with selected tumor indications. New recruitment is open for all active cohorts. Active cohorts: Escalation revised dosing regimen cohort. Closed cohorts: Non-small cell lung cancer (NSCLC, first line), NSCLC (post-platinum), metastatic breast cancer (MBC), colorectal cancer (CRC), urothelial carcinoma (secondary), mesothelioma, gastric/GEJ cancer (first line switch maintenance and second line), and ovarian cancer (secondary and platinum refractory + liposomal doxorubicin), renal cell carcinoma (second line) melanoma and head, neck squamous cell carcinoma (HNSCC), castrate-resistant prostate cancer (CRPC), adrenocortical carcinoma (ACC) urothelial carcinoma (efficacy), gastric/gastroesophageal junction (GEJ) cancer (third line), renal cell carcinoma (RCC, first line) and escalation phase .

Related Conditions:
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Avelumab in Metastatic or Locally Advanced Solid Tumors (JAVELIN Solid Tumor)
  • Official Title: A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of Avelumab (MSB0010718C) in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications

Clinical Trial IDs

  • ORG STUDY ID: EMR 100070-001
  • SECONDARY ID: 2013-002834-19
  • NCT ID: NCT01772004

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
AvelumabMSB0010718C, Anti PD-L1Avelumab

Purpose

This is a Phase 1, open-label, dose-escalation trial of avelumab [antibody targeting programmed death ligand 1 (anti PD-L1)] with consecutive parallel group expansion in subjects with selected tumor indications. New recruitment is open for all active cohorts. Active cohorts: Escalation revised dosing regimen cohort. Closed cohorts: Non-small cell lung cancer (NSCLC, first line), NSCLC (post-platinum), metastatic breast cancer (MBC), colorectal cancer (CRC), urothelial carcinoma (secondary), mesothelioma, gastric/GEJ cancer (first line switch maintenance and second line), and ovarian cancer (secondary and platinum refractory + liposomal doxorubicin), renal cell carcinoma (second line) melanoma and head, neck squamous cell carcinoma (HNSCC), castrate-resistant prostate cancer (CRPC), adrenocortical carcinoma (ACC) urothelial carcinoma (efficacy), gastric/gastroesophageal junction (GEJ) cancer (third line), renal cell carcinoma (RCC, first line) and escalation phase .

Trial Arms

NameTypeDescriptionInterventions
AvelumabExperimental
  • Avelumab

Eligibility Criteria

        Inclusion Criteria for dose escalation and expansion phase:

          -  Signed written informed consent

          -  Male or female subjects aged greater than or equal to 18 years

          -  Subjects must have histologically or cytologically proven metastatic or locally
             advanced solid tumors, for which no standard therapy exists or standard therapy has
             failed. Availability of tumor archival material or fresh biopsies is optional for
             subjects in dose escalation

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at trial entry
             and an estimated life expectancy of at least 3 months

          -  Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST
             1.1, except for subjects with metastatic castrate-resistant prostate cancer (mCRPC) or
             metastatic breast cancer (MBC) who may be enrolled with objective evidence of disease
             without a measureable lesion

          -  Adequate hematological, hepatic and renal function as defined in the protocol

          -  Effective contraception for both male and female subjects if the risk of conception
             exists

          -  Other protocol defined inclusion criteria could apply

        Inclusion Criteria for expansion phase:

          -  Subjects must have relapsed, refractory, or progressive disease following last line of
             treatment (with the exception of the gastric and gastroesophageal junction (GEJ)
             cancer cohort, which does not require progression). Availability of tumor archival
             material or fresh biopsies (excluding bone biopsies) is mandatory for eligibility in
             the expansion cohorts. For subjects in the MBC cohort, the biopsy or surgical specimen
             must have been collected within 90 days prior to the first investigational medicinal
             product (IMP) administration. Specifically, the following will be required:

          -  NSCLC post platinum doublet: Histologically or cytologically confirmed stage IIIB or
             stage IV NSCLC that has progressed after 1 line of platinum-containing doublet
             chemotherapy. Subjects should have received only 1 line of platinum-containing
             treatment for metastatic disease (i.e., adjuvant treatment with a platinum-containing
             regimen is not sufficient for eligibility because not received in the context of a
             metastatic disease). Subjects in the NSCLC cohort will only be enrolled in USA

          -  NSCLC first line: Stage IV (per 7th International Association for the Study of Lung
             Cancer [IASLC] classification) or recurrent NSCLC that is histologically proven.
             Subjects must not have received treatment for their metastatic or recurrent disease.
             No activating epidermal growth factor receptor (EGFR) mutation nor ALK
             translocation/re-arrangement

          -  Gastric and GEJ cancer: Histologically confirmed, unresectable locally advanced or
             metastatic adenocarcinoma of the gastric and gastro-esophageal junction, treated with
             first-line chemotherapy combination with or without disease progression. Subjects
             should have received no more than 1 line of treatment for metastatic disease. Subjects
             should not have been treated with trastuzumab (but can be Human Epidermal growth
             factor Receptor 2 [HER2] positive). Subjects who received any platinum containing
             doublet or triplet as a neoadjuvant chemotherapy strategy, but are not ultimately
             candidates for surgery will also be eligible, as long as they did not have progressive
             disease after completion of the neoadjuvant chemotherapy. In addition, subjects with
             gastric cancer can enter in the study if their white blood cell (WBC) and lymphocyte
             count is as defined in the protocol

          -  MBC: Subjects must have histologically confirmed locally advanced or MBC and have
             tumor that is refractory to or progressive after standard of care therapy. Subjects
             must have received no more than 3 prior lines of cytotoxic therapy for metastatic
             disease. Subjects must have received a taxane and an anthracycline, unless
             contra-indicated

          -  Secondary expansion cohorts: Metastatic colorectal cancer (mCRC), Metastatic
             castrate-resistant prostate cancer (mCRPC), melanoma, ovarian cancer, ACC,
             mesothelioma, urothelial carcinoma and renal cell carcinoma as defined in the protocol

          -  Efficacy expansion cohorts: Gastric and GEJ cancer (third line), ovarian cancer
             (platinum Refractory + liposomal doxorubicin), urothelial carcinoma, and HNSCC as
             defined in the protocol

               -  Other protocol defined inclusion criteria for expansion phase could apply

        Exclusion Criteria for dose escalation and expansion phase:

          -  Concurrent treatment with a non-permitted drug

          -  Prior therapy with specific antibody/drug targeting T cell co-regulatory proteins
             (immune checkpoints)

          -  Concurrent anticancer treatment, major surgery, or use of any investigational drug
             within 28 days before the start of trial treatment; or concurrent systemic therapy
             with immunosuppressive agents, use of hormonal agents within 7 days before the start
             of trial treatment as defined in the protocol. Note: Subjects receiving bisphosphonate
             or denosumab are eligible provided treatment was initiated at least 14 days before the
             first dose of avelumab.

          -  Previous malignant disease other than the target malignancy to be investigated in this
             trial within the last 5 years with the exception of basal or squamous cell carcinoma
             of the skin or cervical carcinoma in situ

          -  Rapidly progressive disease (for example, tumor lysis syndrome)

          -  Active or history of central nervous system metastases

          -  Receipt of any organ transplantation including allogeneic stem-cell transplantation

          -  Significant acute or chronic infections as defined in the protocol

          -  Active or history of any autoimmune disease (subjects with diabetes Type 1, vitiligo,
             psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are
             eligible) or immunodeficiencies

          -  Known severe hypersensitivity reactions to monoclonal antibodies, any history of
             anaphylaxis, or uncontrolled asthma

          -  Persisting toxicity related to prior therapy greater than Grade 1 NCI-CTCAE v4.0,
             however sensory neuropathy less than or equal to Grade 2 is acceptable

          -  Pregnancy or lactation period

          -  Known alcohol or drug abuse

          -  Clinically significant (that is, active) cardiovascular disease

          -  All other significant diseases (for example, inflammatory bowel disease), which, in
             the opinion of the investigator, might impair the subject's tolerance of trial
             treatment

          -  Any psychiatric condition that would prohibit the understanding or rendering of
             informed consent

          -  Legal incapacity or limited legal capacity

          -  Non-oncology vaccine therapies for prevention of infection disease (for example,
             seasonal flu vaccine, human papilloma virus vaccine) within 4 weeks of study drug
             administration. Vaccination while on study is also prohibited except for
             administration of the inactivated influenza vaccine
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicity
Time Frame:Up to 3 weeks
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of subjects with Treatment-Emergent Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0
Time Frame:Screening up to 10 weeks after last treatment
Safety Issue:
Description:
Measure:Pharmacokinetic parameters: AUC (0-t), AUC (0-infinity), λz, Cmax, Tmax, T(1/2) of avelumab
Time Frame:Every 6-week up to Week 25
Safety Issue:
Description:
Measure:Immune-related Best Overall Response (irBOR) and Best Overall Response (BOR) according to modified Immune-related response criteria (irRC) and RECIST version 1.1, respectively
Time Frame:Time from inclusion in the trial until the date of first documented progression or discontinuation from the study due to any cause, up to 1 year after last treatment
Safety Issue:
Description:
Measure:Immune-related Progression-Free Survival (irPFS) time and Progression-Free Survival (PFS) Time according to modified irRC and RECIST version 1.1 , respectively
Time Frame:Time from inclusion in the trial until first observation of progressive disease or death when death occurs within 12 weeks of the last tumor assessment or first administration of trial treatment (whichever is later) up to 1 year after last treatment
Safety Issue:
Description:
Measure:Overall Survival Time
Time Frame:Time from randomization to death anticipated up to 2 years after last treatment
Safety Issue:
Description:
Measure:Pharmacodynamic profile of avelumab to include serum levels of cytokines
Time Frame:Up to Week 25
Safety Issue:
Description:
Measure:Number of subjects with anti-avelumab antibodies
Time Frame:Every 6-week up to Week 25
Safety Issue:
Description:
Measure:Level of PD-L1 tumor expression
Time Frame:Every 6-week up to Week 25
Safety Issue:
Description:
Measure:Unconfirmed response according to RECIST 1.1 per investigator assessment for Primary expansion cohort
Time Frame:Week 13
Safety Issue:
Description:
Measure:Duration of response according to modified irRC and RECIST 1.1 per investigator assessment
Time Frame:Time from inclusion in the trial until the date of first documented disease progression or discontinuation from the study due to any cause, up to 1 year after last treatment
Safety Issue:
Description:
Measure:Progression Free Survival time according to RECIST 1.1 for Efficacy Expansion Cohorts
Time Frame:Time from inclusion in the trial until the date of first documented disease progression or discontinuation from the study due to any cause, up to 1 year after last treatment
Safety Issue:
Description:
Measure:Duration of response according to RECIST 1.1 for Efficacy Expansion cohorts
Time Frame:Time from inclusion in the trial until the date of first documented disease progression or discontinuation from the study due to any cause, up to 1 year after last treatment
Safety Issue:
Description:
Measure:Confirmed BOR as per RECIST 1.1 as adjudicated by an Independent Endpoint Review Committee (IERC) for secondary urothelial carcinoma cohort
Time Frame:Time Frame: Every 6 weeks for first 12 months, then 12-weekly until end of treatment and post treatment every 3 months ( up to 52 months)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:EMD Serono

Trial Keywords

  • Solid Tumors
  • MSB0010718C
  • Phase 1
  • Pharmacokinetic
  • anti PD-L1
  • Non-small cell lung cancer (NSCLC)
  • Metastatic breast cancer (MBC)
  • Gastric and gastroesophageal junction (GEJ) cancer
  • Ovarian cancer
  • Colorectal cancer (CRC)
  • Castrate-resistant prostate cancer (CRPC)
  • Melanoma
  • Urothelial carcinoma
  • Bladder cancer
  • Head and neck squamous cell carcinoma (HNSCC)
  • Renal cell carcinoma (RCC)
  • Adrenocortical carcinoma (ACC)

Last Updated

February 28, 2018