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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02554812




Registration number
NCT02554812
Ethics application status
Date submitted
16/09/2015
Date registered
18/09/2015
Date last updated
14/10/2019

Titles & IDs
Public title
A Study Of Avelumab In Combination With Other Cancer Immunotherapies In Advanced Malignancies (JAVELIN Medley)
Scientific title
A PHASE 1B/2 OPEN-LABEL STUDY TO EVALUATE SAFETY, CLINICAL ACTIVITY, PHARMACOKINETICS AND PHARMACODYNAMICS OF AVELUMAB (MSB0010718C) IN COMBINATION WITH OTHER CANCER IMMUNOTHERAPIES IN PATIENTS WITH ADVANCED MALIGNANCIES
Secondary ID [1] 0 0
2015-002552-27
Secondary ID [2] 0 0
B9991004
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avelumab
Treatment: Drugs - Utomilumab
Treatment: Drugs - PF-04518600
Treatment: Drugs - PD 0360324
Treatment: Drugs - CMP-001

Experimental: Cohort A1 - NSCLC patients treated with avelumab + utomilumab (Dose level 1)

Experimental: Cohort A2 - NSCLC patients treated with avelumab + utomilumab (Dose level 2)

Experimental: Cohort A3 - NSCLC patients treated with avelumab + utomilumab (Dose level 3)

Experimental: Cohort A4 - Melanoma patients treated with avelumab +utomilumab

Experimental: Cohort A5 - SCCHN patients treated with avelumab + utomilumab

Experimental: Cohort A6 - TNBC patients treated with avelumab + utomilumab

Experimental: Cohort A7 - SCLC that has progressed after at least 1 line of platinum-containing therapy treated with avelumab +utomilumab

Experimental: Cohort A8 - NSCLC first-line Stage IV treated with avelumab +PF-05082566

Experimental: Combination B Dose Escalation - PF-04518600 + avelumab in selected tumor types

Experimental: Combination B Expansion Cohorts - PF-04518600 + avelumab in selected tumor types

Experimental: Combination C Dose escalation cohorts - PD 0360324 + avelumab in selected tumor types

Experimental: Combination C Dose expansion cohorts - PD 0360324 + aveluamb in selected tumor types

Experimental: Combination D Dose escalation cohorts - PF-05082566 + PF-04518600 + avelumab in selected tumor types

Experimental: Combination D Dose expansion cohorts - PF-05082566 + PF-04518600 + avelumab in selected tumor types

Experimental: Cohort A9 - NSCLC first-line Stage IV treated with avelumab +utomilumab (sequential starting with utomilumab monotherapy followed by combination)

Experimental: Cohort A10 - NSCLC first-line Stage IV treated with avelumab + utomilumab (sequential starting with avelumab monotherapy followed by combination)

Experimental: Cohort F1 - CMP-001 +avelumab in SCCHN

Experimental: Cohort F2 - CMP-001+avelumab+utomilumab in SCCHN

Experimental: Cohort F3 - CMP-001 +avelumab+PF-04518600 in SCCHN


Treatment: Drugs: Avelumab
Anti-PD-L1 antibody

Treatment: Drugs: Utomilumab
Anti-4-1BB antibody

Treatment: Drugs: PF-04518600
OX40 Agonist

Treatment: Drugs: PD 0360324
Anti-M-CSF

Treatment: Drugs: CMP-001
TLR9 agonist

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with Dose-Limiting Toxicities (DLT) - For Phase 1b: DLTs for Combination A (avelumab and PF-05082566) or Combination B (avelumab and PF-04518600) or Combination C (avelumab and PD 0360324) or Combination D (Avelumab and utomilumab and PF-04518600)occurring during the first 8 weeks of treatment (first 2 cycles). For Phase 1b: DLT for Combination F (avelumab plus CMP-001 and utomilumab or PF-04518600) occurring during the first 4 weeks of treatment (first cycle).
Timepoint [1] 0 0
First 8 weeks of treatment (Combination A-D) First 4 weeks of treatment (CombinationF)
Primary outcome [2] 0 0
Objective Response - Number of Participants With Objective Response - For Phase 2: Number of participants with objective response (ie, confirmed complete or partial response according to RECIST Version 1.1).
Timepoint [2] 0 0
Baseline up to approximately 24 months
Secondary outcome [1] 0 0
Cmax of avelumab (MSB0010718C) - Cmax defined as the maximum plasma concentration of avelumab (MSB0010718C)
Timepoint [1] 0 0
Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, then on Day 1 of Cycles 2, 4, 6, and 10
Secondary outcome [2] 0 0
Cmax of PF-05082566 - Cmax defined as the maximum plasma concentration of PF-05082566
Timepoint [2] 0 0
Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, and then on Day 1 of Cycles 3, 5, 8, and 12
Secondary outcome [3] 0 0
Ctrough of avelumab (MSB0010718C) - Ctrough is defined as the trough plasma concentration at the end of an avelumab dosage interval.
Timepoint [3] 0 0
Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, then on Day 1 of Cycles 2, 4, 6, and 10
Secondary outcome [4] 0 0
Ctrough of PF-05082566 - Ctrough is defined as the trough plasma concentration at the end of a PF-05082566 dosage interval.
Timepoint [4] 0 0
Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, and then on Day 1 of Cycles 3, 5, 8, and 12
Secondary outcome [5] 0 0
Anti-Drug Antibody (ADA) levels of avelumab (MSB0010718C) - Immunogenicity assessment of avelumab (MSB0010718C).
Timepoint [5] 0 0
Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 10
Secondary outcome [6] 0 0
Anti-Drug Antibody (ADA) levels of PF-05082566 - Immunogenicity assessment of PF-05082566.
Timepoint [6] 0 0
Pre-dose on Day 1 of Cycles 1, 3, 5, 8, and 12
Secondary outcome [7] 0 0
Time to Tumor Response (TTR) - Time to Tumor Response (TTR) is defined for patients with confirmed objective response (CR or PR) as the time from the date of randomization (NSCLC) or date of first dose of study treatment (melanoma and SCCHN) to the first documentation of objective tumor response.
Timepoint [7] 0 0
Baseline up to approximately 24 months
Secondary outcome [8] 0 0
Duration of Response (DR) - Duration of Response (DR) is defined for patients with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
Timepoint [8] 0 0
Baseline up to approximately 24 months
Secondary outcome [9] 0 0
Progression-Free Survival (PFS) - Progression-Free Survival (PFS) is defined as the time from the date of randomization (NSCLC) or date of first dose of study treatment (melanoma and SCCHN) to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurs first.
Timepoint [9] 0 0
Baseline up to approximately 24 months
Secondary outcome [10] 0 0
Overall Survival (OS) - Overall Survival (OS) is defined as the time from the date of randomization (NSCLC) or date of first dose of study treatment (melanoma and SCCHN) to the date of death.
Timepoint [10] 0 0
Baseline up to approximately 24 months
Secondary outcome [11] 0 0
Tumor tissue biomarkers - Tumor tissue biomarkers, including, but not limited to, PD-L1 expression and tumor infiltrating CD8+ T lymphocytes
Timepoint [11] 0 0
Baseline
Secondary outcome [12] 0 0
Cmax of PF-04518600 - Cmax defined as the maximum plasma concentration of PF-04518600
Timepoint [12] 0 0
Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, then on Day 1 of Cycles 2, 4, 6, and 10
Secondary outcome [13] 0 0
Anti-Drug Antibody (ADA) levels of PF-04518600 - Immunogenicity assessment of PF-04518600.
Timepoint [13] 0 0
Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 10
Secondary outcome [14] 0 0
Ctrough of PF-04518600 - Ctrough is defined as the trough plasma concentration at the end of a PF-04518600 dosage interval.
Timepoint [14] 0 0
Pre-dose and 1 hour post-dose on Days 1, 8, and 15 of Cycle 1, then on Day 1 of Cycles 2, 4, 6, and 10

Eligibility
Key inclusion criteria
- Histological or cytological diagnosis of advanced/metastatic solid tumor. Measurable
disease by RECIST 1.1 with at least 1 measurable lesion that has not been previously
irradiated. Availability of tumor specimen taken within 1 year prior to study entry,
with no intervening systemic anti-cancer therapy. No prior PD-1/PDL-1 therapy allowed.
Combination A: Phase 1b, patients with NSCLC that have progressed on standard therapy
or for which no standard therapy is available, and Phase 2, patients with NSCLC,
melanoma, SCCHN, TNBC in any line of therapy, SCLC, 1st line NSCLC. 1st line NSCLC
must demonstrate to express PD-L1. Activating EGFR mutation, ALK, ROS1
translocation/rearrangements are not permitted. Combination B: Phase 1b, patients with
advanced solid tumors (NSCLC, SCCHN, melanoma) that have progressed on standard
therapy or for which no standard therapy is available, and Phase 2, patients with
NSCLC, melanoma, or SCCHN. Up to 2 lines of prior therapy in advanced/metastatic
disease setting allowed. Activating EGFR mutation, ALK, ROS1
translocation/rearrangements are not permitted. Combination C: Ovarian cancer, SCCHN,
NSCLC, gastric cancer, platinum resistant ovarian cancer. Up to 2 lines of prior
therapy in advanced/metastatic disease setting allowed. TGCT/PVNS that is either
inoperable or requires extensive resection. Prior treatment with agents targeting
CSF-1/CSF-1R not allowed. NSCLC activating EGFR mutation, ALK, ROS1
translocation/rearrangements are not permitted. Combination D: NSCLC, melanoma, SCCHN,
bladder cancer. NSCLC activating EGFR mutation, ALK, ROS1 translocation/rearrangements
are not permitted. Up to 2 lines of prior therapy in advanced/metastatic disease
setting allowed. Combination F: Recurrent or metastatic SCCHN. One to three prior
lines of systemic therapy for advanced stage or metastatic disease. Patients must have
received anti PD-1/PD-L1 containing therapy as the last systemic cancer treatment,
with disease progression no earlier than 6 weeks from initiation of therapy. The last
dose of prior PD-1/PD-L1 agent must be no more than 24 weeks from patient enrollment
with no intervening therapy. Evidence of radiologic progression is required. Patient
must have at least one injectable tumor lesion

- ECOG performance status 0 or 1

- Estimated life expectancy of at least 3 months

- Adequate bone marrow, renal, and liver function

- Resolved acute effects of prior therapy

- Negative serum pregnancy test at screening

- Male and female patients able to have children must agree to use at least 1 highly
effective method of contraception throughout the study and for at least 90 days after
last dose

- Signed and dated informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Monoclonal antibody based anti-cancer therapy within 28 days prior to study entry or
small-molecule based anti-cancer therapy (targeted therapy or chemotherapy) within 14
days prior to study entry. Combination F:PD-1/PD-L1 agent within 14 days prior study
entry.

- Current or prior use of immunosuppressive medication within 7 days prior to study
entry

- Active autoimmune disease requiring systemic steroids or immunosuppressive agents
within 7 days prior to study entry

- Known prior or suspected hypersensitivity to investigational products

- Major surgery within 4 weeks or radiation therapy within 14 days prior to study entry

- Patients with known symptomatic brain metastases requiring steroids

- Previous high-dose chemotherapy requiring stem cell rescue

- Prior allogeneic stem cell transplant or organ graft

- Any of the following within 6 months prior to study entry: myocardial infarction,
uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive
heart failure, cerebrovascular accident, or transient ischemic attack

- Symptomatic pulmonary embolism within 6 months prior to study entry

- Known HIV or AIDS-related illness

- Active infection requiring systemic therapy

- Positive HBV or HCV test indicating acute or chronic infection

- Administration of a live vaccine within 4 weeks prior to study entry

- Diagnosis of other malignancy within 5 years, except for adequately treated basal cell
or squamous cell skin cancer, or carcinoma in situ of the breast or cervix, or
low-grade (Gleason =6) prostate cancer

- Participation in other studies involving investigational drug(s) within 4 weeks prior
to study entry and/or during study participation

- Persisting toxicity related to prior therapy >Grade 1

- Other severe acute or chronic medical condition

- Combo C :Existing periorbital edema.

- Combo C : Hypocalcemia, clinically significant bone disease or recent bone fracture
(within 12 weeks prior study entry)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse Pharmacy - Camperdown
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [3] 0 0
Macquarie University Hospital Pharmacy - Macquarie University
Recruitment hospital [4] 0 0
Macquarie University - Macquarie University
Recruitment hospital [5] 0 0
The Mater Hospital - North Sydney
Recruitment hospital [6] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [7] 0 0
Baxter Healthcare - Old Toongabie
Recruitment hospital [8] 0 0
Brighton Medical Imaging - Brighton
Recruitment hospital [9] 0 0
Cabrini Hospital Brighton - Brighton
Recruitment hospital [10] 0 0
Austin Health - Heidelberg
Recruitment hospital [11] 0 0
Cabrini Hospital Malvern - Malvern
Recruitment hospital [12] 0 0
Cabrini Hospital - Malvern
Recruitment hospital [13] 0 0
Malvern Medical Imaging - Malvern
Recruitment hospital [14] 0 0
Pharmacy - Malvern
Recruitment hospital [15] 0 0
Macquarie Heart - New South Wales
Recruitment hospital [16] 0 0
Macquarie Medical Imaging - New South Wales
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2109 - Macquarie University
Recruitment postcode(s) [3] 0 0
2060 - North Sydney
Recruitment postcode(s) [4] 0 0
2065 - North Sydney
Recruitment postcode(s) [5] 0 0
2146 - Old Toongabie
Recruitment postcode(s) [6] 0 0
3186 - Brighton
Recruitment postcode(s) [7] 0 0
3084 - Heidelberg
Recruitment postcode(s) [8] 0 0
3144 - Malvern
Recruitment postcode(s) [9] 0 0
2109 - New South Wales
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Iowa
Country [5] 0 0
United States of America
State/province [5] 0 0
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Rhode Island
Country [10] 0 0
United States of America
State/province [10] 0 0
South Dakota
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Quebec
Country [18] 0 0
France
State/province [18] 0 0
Cedex
Country [19] 0 0
Japan
State/province [19] 0 0
Chiba
Country [20] 0 0
Japan
State/province [20] 0 0
Tokyo
Country [21] 0 0
Poland
State/province [21] 0 0
Mazowieckie
Country [22] 0 0
Poland
State/province [22] 0 0
Wielkopolskie
Country [23] 0 0
Taiwan
State/province [23] 0 0
Taipei
Country [24] 0 0
United Kingdom
State/province [24] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a Phase 1b/2 dose-optimization study to evaluate safety, pharmacokinetics,
pharmacodynamics, and preliminary antitumor activity of avelumab (MSB0010718C) in combination
with other cancer immunotherapies in patients with locally advanced or metastatic solid
tumors. The primary purpose is to assess the safety and early signs of efficacy of various
avelumab combinations with other cancer immunotherapies, optimizing dosing regimens as
appropriate, in a limited series of indications.
Trial website
https://clinicaltrials.gov/show/NCT02554812
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Country 0 0
Phone 0 0
1-800-718-1021
Fax 0 0
Email 0 0
ClinicalTrials.gov_Inquiries@pfizer.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02554812