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

NCT ID: NCT01943461

Last Updated: 2020-09-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-02
• Study Completion Date: 2019-09-25

Brief Summary

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.

Conditions

Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose-escalation Cohort: Avelumab 3 mg/kg

Group Type: EXPERIMENTAL

Avelumab 3 mg/kg

Intervention Type: DRUG

Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 3 milligrams per kilogram (mg/kg) once every 2 weeks in the dose- escalation cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred.

Dose-escalation Cohort: Avelumab 10 mg/kg

Group Type: EXPERIMENTAL

Avelumab 10 mg/kg

Intervention Type: DRUG

Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 10 mg/kg once every 2 weeks in the dose- escalation cohort and expansion cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred.

Dose-escalation Cohort: Avelumab 20 mg/kg

Group Type: EXPERIMENTAL

Avelumab 20 mg/kg

Intervention Type: DRUG

Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 20 mg/kg once every 2 weeks in the dose- escalation cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred.

Expansion Cohort: Avelumab 10 mg/kg

Group Type: EXPERIMENTAL

Avelumab 10 mg/kg

Intervention Type: DRUG

Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 10 mg/kg once every 2 weeks in the dose- escalation cohort and expansion cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred.

Interventions

Avelumab 10 mg/kg

Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 10 mg/kg once every 2 weeks in the dose- escalation cohort and expansion cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred.

Intervention Type: DRUG

Avelumab 20 mg/kg

Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 20 mg/kg once every 2 weeks in the dose- escalation cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred.

Intervention Type: DRUG

Avelumab 3 mg/kg

Participants received intravenous infusion of Avelumab over 1 hour duration at a dose of 3 milligrams per kilogram (mg/kg) once every 2 weeks in the dose- escalation cohort until disease progression, unacceptable toxicity or withdrawal from the study or study drug occurred.

Intervention Type: DRUG

Other Intervention Names

anti PD-L1; MSB0010718C

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

Research site

Darmstadt, , Germany

Countries

Germany

References

Doi T, Iwasa S, Muro K, Satoh T, Hironaka S, Esaki T, Nishina T, Hara H, Machida N, Komatsu Y, Shimada Y, Otsu S, Shimizu S, Watanabe M. Phase 1 trial of avelumab (anti-PD-L1) in Japanese patients with advanced solid tumors, including dose expansion in patients with gastric or gastroesophageal junction cancer: the JAVELIN Solid Tumor JPN trial. Gastric Cancer. 2019 Jul;22(4):817-827. doi: 10.1007/s10120-018-0903-1. Epub 2018 Dec 4.

Reference Type: BACKGROUND

PMID: 30515672 (View on PubMed)

Novakovic AM, Wilkins JJ, Dai H, Wade JR, Neuteboom B, Brar S, Bello CL, Girard P, Khandelwal A. Changing Body Weight-Based Dosing to a Flat Dose for Avelumab in Metastatic Merkel Cell and Advanced Urothelial Carcinoma. Clin Pharmacol Ther. 2020 Mar;107(3):588-596. doi: 10.1002/cpt.1645. Epub 2019 Nov 18.

Reference Type: DERIVED

PMID: 31553054 (View on PubMed)

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=EMR100070-002

Trial Awareness and Transparency website

http://www.merckgroup.com/en/company/contact-us/medinfo-contact-map.html

Medical Information Location Map - Med Info Contacts

Other Identifiers

EMR 100070-002

Identifier Type: -

Identifier Source: org_study_id