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

NCT01943461 | Completed Phase 1 Results

• 1 other identifier: EMR 100070-002
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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

Keywords

Solid Tumors; MSB0010718C; anti PD-L1; avelumab; Phase 1

Outcome Measures

Primary Outcomes (1)

• Dose-escalation Cohorts: Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT: any Grade greater than or equal to (\>=) 3 or Adverse Events (AE) according to National Cancer Institute Common Toxicity Criteria for AE Version 4.03 (NCI-CTCAE v4.03); observed during first 3 weeks of dose-escalation part and as being related to Avelumab by Investigator/Sponsor. Following events were not considered as DLT: Grade 3 infusion-related reaction resolving to (\<=) Grade 1 within 6 hours and controlled with medical management; Transient (\<=6 hours) Grade 3 flulike symptoms/fever controlled with medical management and resolved to \<= Grade 1;Transient (\<=24 hours) Grade 3 fatigue, local reactions, headache, nausea, emesis that resolved to \<=Grade1 with/without medical management, Grade 3 diarrhea, Grade 3 skin toxicity, Grade3 out-of-range laboratory values without any clinical correlate that resolves to \<= Grade 1 or Baseline in \< 7 days after medical management; Tumor flare phenomenon defined as local pain, irritation, rash localized at sites of known or suspected tumor.

  Baseline up to 3 weeks

Secondary Outcomes (23)

• Dose-escalation Cohorts: Area Under the Serum Concentration-Time Curve From the Time of Dosing to the Time of the Last Observation (AUC0-t) of Avelumab

  Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion

• Dose-escalation Cohorts: Area Under the Serum Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Avelumab

  Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion

• Dose-escalation Cohorts: Maximum Observed Serum Concentration (Cmax) of Avelumab

  Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion

• Dose-escalation Cohorts: Time to Reach Maximum Observed Serum Concentration (Tmax) of Avelumab

  Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion

• Dose-escalation Cohorts: Terminal Half-Life (t1/2) of Avelumab

  Within 6 hours before the infusion, at end of 1-hour infusion (Day 1), 0.5, 1, 2, 4, 6,12, 24, 36, 48, 168 hours after end of infusion

Study Arms (4)

Dose-escalation Cohort: Avelumab 3 mg/kg

EXPERIMENTAL

Drug: Avelumab 3 mg/kg

Dose-escalation Cohort: Avelumab 10 mg/kg

EXPERIMENTAL

Drug: Avelumab 10 mg/kg

Dose-escalation Cohort: Avelumab 20 mg/kg

EXPERIMENTAL

Drug: Avelumab 20 mg/kg

Expansion Cohort: Avelumab 10 mg/kg

EXPERIMENTAL

Drug: Avelumab 10 mg/kg

Interventions

Avelumab 3 mg/kg 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.

Also known as: anti PD-L1, MSB0010718C

Dose-escalation Cohort: Avelumab 3 mg/kg

Avelumab 10 mg/kg 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 10 mg/kg; Expansion Cohort: Avelumab 10 mg/kg

Avelumab 20 mg/kg 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.

Dose-escalation Cohort: Avelumab 20 mg/kg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (1)

Research site

Darmstadt, Germany

Location

Related Publications (2)

• 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.

  PMID: 30515672 BACKGROUND

• 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.

  PMID: 31553054 DERIVED

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Interventions

avelumab

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2013
• First Posted: September 17, 2013
• Study Start: September 2, 2013
• Primary Completion: January 7, 2015
• Study Completion: September 25, 2019
• Last Updated: September 30, 2020
• Results First Posted: September 30, 2020

Record last verified: 2020-09

Locations

DE (1)