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

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 1

Conditions: Solid Tumors

Treatments: Drug: Avelumab 10 mg/kg; Drug: Avelumab 20 mg/kg; Drug: Avelumab 3 mg/kg

Study type: Interventional

Funder types: Industry

Identifiers

NCT01943461

EMR 100070-002

Details and patient eligibility

About

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

Enrollment: 57 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed written informed consent

• Male or female participants 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

  • Participants should not have severe peritoneal metastases. The following criteria were applied:

    • No clinical ileus or subileus
    • No moderate-to-severe ascites (participants 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 participants 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 participant'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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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57 participants in 4 patient groups

Dose-escalation Cohort: Avelumab 3 mg/kg

Experimental group

Treatment:

Drug: Avelumab 3 mg/kg

Dose-escalation Cohort: Avelumab 10 mg/kg

Experimental group

Treatment:

Drug: Avelumab 10 mg/kg

Dose-escalation Cohort: Avelumab 20 mg/kg

Experimental group

Treatment:

Drug: Avelumab 20 mg/kg

Expansion Cohort: Avelumab 10 mg/kg

Experimental group

Treatment:

Drug: Avelumab 10 mg/kg