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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01943461
Recruitment Status : Active, not recruiting
First Posted : September 17, 2013
Last Update Posted : December 14, 2018
Information provided by (Responsible Party):
Merck KGaA, Darmstadt, Germany

Brief Summary:
This is a Phase 1, open-label, dose-escalation trial of avelumab (antibody targeting programmed death ligand 1 [anti PD-L1]) in Japanese subjects with metastatic or locally advanced solid tumors, followed by a consecutive expansion part in Asian subjects with gastric cancer.

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: Avelumab Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 57 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Trial to Investigate the Tolerability, Safety, Pharmacokinetics, Biological and Clinical Activity of Avelumab (MSB0010718C) in Japanese Subjects With Metastatic or Locally Advanced Solid Tumors, With Expansion Part in Asian Subjects With Gastric Cancer
Actual Study Start Date : September 2, 2013
Actual Primary Completion Date : January 7, 2015
Estimated Study Completion Date : April 30, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arm Intervention/treatment
Experimental: Avelumab Drug: Avelumab
Avelumab will be administered in study location using a protocol-defined dose escalation scheme until confirmed complete response (CR), confirmed progression, unacceptable toxicity, or withdrawal from the trial or investigational medicinal product (IMP) occurs.
Other Names:
  • anti PD-L1
  • MSB0010718C

Primary Outcome Measures :
  1. Dose Limiting Toxicity [ Time Frame: Up to 3 weeks ]

Secondary Outcome Measures :
  1. Area under the concentration-time curve from the time of dosing to the time of the last observation AUC (0-t) [ Time Frame: Every 6-week up to Week 25 ]
  2. Area under the curve from the time of dosing extrapolated to infinity (AUC [0-infinity]) [ Time Frame: Every 6-week up to Week 25 ]
  3. Terminal elimination rate constant (λz) [ Time Frame: Every 6-week up to Week 25 ]
  4. Maximum observed serum concentration (Cmax) [ Time Frame: Every 6-week up to Week 25 ]
  5. Time to reach maximum observed serum concentration (Tmax) [ Time Frame: Every 6-week up to Week 25 ]
  6. Elimination Half-Life t(1/2) [ Time Frame: Every 6-week up to Week 25 ]
  7. Level of programmed death ligand 1 (PD-L1) tumor expression [ Time Frame: Every 6-week up to Week 25 ]
  8. Evaluation of biologic response by receptor occupancy of avelumab [ Time Frame: Days 1, 3, 15, 29, 43 and 85 ]
  9. Immune-related Best Overall Response (irBOR) and Best Overall Response (BOR) according to modified Immune-related response criteria (irRC) and Response Evaluation Criteria in Solid Tumors (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 ]
  10. 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 ]
  11. Overall Survival Time [ Time Frame: Time from first treatment to death anticipated up to 1 year after last treatment ]
  12. Number of subjects with anti-avelumab antibodies [ Time Frame: Every 6-week up to Week 25 ]
  13. 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 28 days after last treatment ]

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Signed written informed consent
  • Male or female subjects aged greater than or equal to (>=) 20 years
  • For dose escalation part: Histologically or cytologically proven metastatic or locally advanced solid tumors, for which no standard therapy exists or standard therapy has failed
  • For expansion part:

    • Availability of fresh and archive tumor in formalin fixed paraffin embedded tissue
    • With histologically or cytologically confirmed recurrent or refractory unresectable Stage IV gastric or gastro-esophageal junctional adenocarcinoma (according to American Joint Committee on Cancer/Union Internationale Contre le Cancer [UICC] 7th edition) and whose disease progressed after one or two prior chemotherapy regimen(s) involving both fluoropyrimidines and platinum
    • Presence of at least 1 measurable lesion according to RECIST version 1.1
    • Subjects should not have severe peritoneal metastases. The following criteria were applied:

      • No clinical ileus or subileus
      • No moderate-to-severe ascites (subjects with ascites restricted to the perihepatic space or pelvic cavity)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 at the trial entry and an estimated life expectancy of at least 3 months
  • Adequate hematological, hepatic and renal function as defined in the protocol
  • All subjects must agree to use effective means of contraception with their partner from entry into the trial through 6 months after the last dose of avelumab

Exclusion Criteria:

  • Concurrent treatment with a non-permitted drug
  • Prior therapy with any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)
  • Concurrent anticancer treatment or concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 30 days before the start of trial treatment. Short-term administration of steroids (that is, for allergic reactions or the management of immune-related adverse events [irAE]) is allowed
  • Previous malignant disease within the last 5 years with the exception of adequately treated non-melanoma skin cancer, in situ cancer, or other cancer
  • Non-oncology vaccine therapies for prevention of infection disease (e.g. 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.
  • 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
  • Other protocol defined exclusion criteria could apply

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 identifier (NCT number): NCT01943461

Please contact the Communication Center
Darmstadt, Germany, 64293
Sponsors and Collaborators
Merck KGaA, Darmstadt, Germany
Study Director: Medical Responsible Merck Serono Co., Ltd., Japan