This trial is active, not recruiting.

Condition solid tumors
Treatment avelumab
Phase phase 1
Target PD-1
Sponsor Merck KGaA
Start date September 2013
End date October 2014
Trial size 57 participants
Trial identifier NCT01943461, EMR 100070-002


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
avelumab anti PD-L1
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.

Primary Outcomes

Dose Limiting Toxicity
time frame: Up to 3 weeks

Secondary Outcomes

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
Area under the curve from the time of dosing extrapolated to infinity (AUC [0-infinity])
time frame: Every 6-week up to Week 25
Terminal elimination rate constant (λz)
time frame: Every 6-week up to Week 25
Maximum observed serum concentration (Cmax)
time frame: Every 6-week up to Week 25
Time to reach maximum observed serum concentration (Tmax)
time frame: Every 6-week up to Week 25
Elimination Half-Life t(1/2)
time frame: Every 6-week up to Week 25
Level of programmed death ligand 1 (PD-L1) tumor expression
time frame: Every 6-week up to Week 25
Evaluation of biologic response by receptor occupancy of avelumab
time frame: Days 1, 3, 15, 29, 43, and 85
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
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
Overall Survival Time
time frame: Time from first treatment to death anticipated up to 1 year after last treatment
Number of subjects with anti-avelumab antibodies
time frame: Every 6-week up to Week 25
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

Eligibility Criteria

Male or female participants at least 20 years old.

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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Merck KGaA.
Location data was received from the National Cancer Institute and was last updated in March 2016.