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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03317496




Registration number
NCT03317496
Ethics application status
Date submitted
29/09/2017
Date registered
23/10/2017
Date last updated
27/05/2020

Titles & IDs
Public title
Safety And Efficacy Study Of Avelumab Plus Chemotherapy With Or Without Other Anti-Cancer Immunotherapy Agents In Patients With Advanced Malignancies
Scientific title
A MULTICENTER, OPEN-LABEL, PHASE 1B/2 STUDY TO EVALUATE SAFETY AND EFFICACY OF AVELUMAB (MSB0010718C) IN COMBINATION WITH CHEMOTHERAPY WITH OR WITHOUT OTHER ANTI-CANCER IMMUNOTHERAPIES AS FIRST-LINE TREATMENT IN PATIENTS WITH ADVANCED MALIGNANCIES
Secondary ID [1] 0 0
B9991023
Secondary ID [2] 0 0
B9991023
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer 0 0
Urothelial Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avelumab 800 mg in combination with pemetrexed / carboplatin
Treatment: Drugs - Avelumab 800 mg in combination with gemcitabine / cisplatin.
Treatment: Drugs - Avelumab 1200 mg in combination with pemetrexed/carboplatin
Treatment: Drugs - Avelumab 1200 mg in combination with gemcitabine/cisplatin

Experimental: Group A Cohort A1 - Non-squamous non-small cell lung cancer (NSCLC) patients treated with 800 mg avelumab plus pemetrexed/carboplatin

Experimental: Group A Cohort A2 - Cisplatin-eligible urothelial cancer (UC)patients treated with 800 mg avelumab plus gemcitabine/cisplatin

Experimental: Group A Cohort A3 - Non-squamous non-small cell lung cancer (NSCLC) patients treated with 1200 mg avelumab plus pemetrexed/carboplatin

Experimental: Group A Cohort A4 - Cisplatin-eligible urothelial cancer (UC) patients treated with 1200 mg avelumab plus gemcitabine/cisplatin


Treatment: Drugs: Avelumab 800 mg in combination with pemetrexed / carboplatin
Avelumab Pemetrexed Carboplatin

Treatment: Drugs: Avelumab 800 mg in combination with gemcitabine / cisplatin.
Avelumab Gemcitabine Cisplatin

Treatment: Drugs: Avelumab 1200 mg in combination with pemetrexed/carboplatin
Avelumab Pemetrexed Carboplatin

Treatment: Drugs: Avelumab 1200 mg in combination with gemcitabine/cisplatin
Avelumab Gemcitabine Cisplatin

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

Outcomes
Primary outcome [1] 0 0
Phase 1b lead-in: Number of patients with dose-limiting toxicities in first 2 cycles - Dose-limiting toxicity rate in first 6 (or 12) patients enrolled in safety Phase 1b lead-in of each cohort
Timepoint [1] 0 0
First 6 weeks of treatment
Primary outcome [2] 0 0
Confirmed objective response (OR) - For each cohort, number of patients in the Phase 1b lead-in and Phase 2 cohort expansion with objective response (confirmed complete or partial response) according to RECIST Version 1.1 from the first dose of study treatment until disease progression or death due to any cause.
Timepoint [2] 0 0
Baseline up to approximately 24 months
Secondary outcome [1] 0 0
Progression-Free Survival (PFS) - Progression-Free Survival (PFS) is defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurs first.
Timepoint [1] 0 0
Baseline up to approximately 24 months
Secondary outcome [2] 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 [2] 0 0
Baseline up to approximately 24 months
Secondary outcome [3] 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 first dose of study treatment to the first documentation of objective tumor response.
Timepoint [3] 0 0
Baseline up to approximately 24 months
Secondary outcome [4] 0 0
Overall Survival (OS) - Overall Survival (OS) is defined as the time from the first dose of study treatment to the date of death.
Timepoint [4] 0 0
Baseline up to approximately 24 months
Secondary outcome [5] 0 0
Plasma concentrations of cisplatin - Pharmacokinetic assessment of cisplatin
Timepoint [5] 0 0
Day 1 and Day 8 of Cycle 2
Secondary outcome [6] 0 0
Plasma concentrations of gemcitabine - Pharmacokinetic assessment of gemcitabine
Timepoint [6] 0 0
Day 1 of Cycle 2
Secondary outcome [7] 0 0
Plasma concentrations of pemetrexed - Pharmacokinetic assessment of pemetrexed
Timepoint [7] 0 0
Day 1 and Day 8 of Cycle 2
Secondary outcome [8] 0 0
Plasma concentrations of carboplatin - Pharmacokinetic assessment of carboplatin
Timepoint [8] 0 0
Day 1 and Day 8 of Cycle 2
Secondary outcome [9] 0 0
Serum concentrations of avelumab - Pharmacokinetic assessment of avelumab
Timepoint [9] 0 0
Pre-dose and 1 hour post-dose on Day 1 of Cycles 1, 2, 3, 6, 10, and 14, and during the Day 15 visit of Cycles 1, 2, and 3
Secondary outcome [10] 0 0
Anti-Drug Antibody (ADA) levels of avelumab - Immunogenicity assessment of avelumab
Timepoint [10] 0 0
Pre-dose on Day 1 of Cycles 1, 2, 3, 6, 10, and 14, and at End of Treatment
Secondary outcome [11] 0 0
Mutational load within baseline tumor tissue - Assessment of the number of mutations present per megabase of DNA within the tumor
Timepoint [11] 0 0
Baseline
Secondary outcome [12] 0 0
PD-L1 expression in baseline and on-treatment tumor tissue - Assessment of PD-L1 expression in tumor tissue obtained prior to treatment with study drug and while on study treatment
Timepoint [12] 0 0
Baseline and Cycle 2 Day 8 (+/- 7 days)

Eligibility
Key inclusion criteria
1. Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid
tumor that is not amenable for treatment with curative intent as follows:

- For all groups:

- Measurable disease by RECIST v1.1 with at least 1 measurable lesion, and
availability of tumor specimen 18 months or less old.

- No prior systemic treatment for unresectable locally advanced or metastatic
disease for the tumor type under study. If prior systemic chemotherapy treatment
was given in the adjuvant or neo-adjuvant setting or as part of radiotherapy
chemotherapy treatment, disease-free interval after stop of systemic treatment
must be more than 6 months for non-squamous NSCLC and more than 12 months for UC;

- Cohort A1 and Cohort A3: Non-squamous NSCLC, with no activating EGFR mutations,
ALK or ROS1 translocations/rearrangements. If monotherapy pembrolizumab is
available as a standard of care treatment option, patients must have a tumor
proportion score (TPS) <50% for PD L1 (via the 22C3 pharmDx or the Ventana
(SP263) PD L1 IHC assay).

- Cohort A2 and Cohort A4: Transitional cell carcinoma of the urothelium including
the bladder, urethra, renal pelvis, and ureter.

2. ECOG performance status 0 or 1

3. Estimated life expectancy of at least 90 days

4. Adequate bone marrow, renal, and liver function

5. Negative serum pregnancy test at screening

6. 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
1. Prior immunotherapy with any antibody or drug specifically targeting T cell
co-stimulation or immune checkpoint pathways.

2. Patients with known symptomatic central nervous system metastases requiring steroids.

3. Diagnosis of other malignancy within 2 years prior to enrollment except adequately
treated basal cell or squamous cell skin cancer, or carcinoma in situ of the bladder,
breast, or cervix, or low grade (Gleason =6) prostate cancer

4. Use of immunosuppressive medication at the time of enrollment

5. Active or prior autoimmune disease that might deteriorate when receiving an
immuno-stimulatory agent.

6. Prior organ transplantation including allogenic stem cell transplantation

7. Active infection requiring systemic therapy

8. Known history of HIV or AIDS

9. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening

10. Administration of live vaccine within 4 weeks prior to study entry

11. Known prior severe hypersensitivity to the investigational products or any component
in their formulations,

12. Known prior severe hypersensitivity to platinum-related compounds for all cohorts, to
pemetrexed for patients enrolled in Cohort A1 and Cohort A3, and to gemcitabine for
patients enrolled in Cohort A2 and Cohort A4

13. Persisting toxicity related to prior therapy (NCI CTCAE v4.03 Grade > 1)

14. Known history of colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis.

15. Ongoing cardiac dysrhythmias of NCI CTCAE v4.03 Grade 2 or prolongation of the QTcF
interval to >480 msec.

16. Clinically significant (ie, active) cardiovascular disease: cerebral vascular
accident/stroke (<6 months prior to enrollment), myocardial infarction (< 6 months
prior to enrollment), unstable angina, congestive heart failure, or serious cardiac
arrhythmia requiring medication.

17. Major surgery =28 days or major radiation therapy =14 days prior to enrollment.

18. Participation in other studies involving investigational drug(s) within 28 days prior
to study entry.

19. Concurrent treatment with a prohibited medication.

20. Other acute or chronic medical or psychiatric condition

21. Pregnant female patients; breastfeeding female patients; fertile male patients and
female patients of childbearing potential who are unwilling or unable to use at least
1 highly effective method of contraception as outlined in this protocol for the
duration of the study and for at least 90 days after the last dose of chemotherapy
(for male and female patients) or at least 30 days after the last dose of avelumab
(for female patients), whichever is longer.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
Parallel
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 - Camperdown
Recruitment hospital [2] 0 0
St Vincent's Public Hospital Sydney - Darlinghurst
Recruitment hospital [3] 0 0
Western Health, Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
3021 - St Albans
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Czechia
State/province [5] 0 0
Czech Republic
Country [6] 0 0
Czechia
State/province [6] 0 0
Olomouc
Country [7] 0 0
Czechia
State/province [7] 0 0
Prague
Country [8] 0 0
Czechia
State/province [8] 0 0
Praha 2
Country [9] 0 0
Czechia
State/province [9] 0 0
Praha 4
Country [10] 0 0
Czechia
State/province [10] 0 0
Praha 5
Country [11] 0 0
Czechia
State/province [11] 0 0
Praha 8
Country [12] 0 0
Hungary
State/province [12] 0 0
Budapest
Country [13] 0 0
Italy
State/province [13] 0 0
AN
Country [14] 0 0
Italy
State/province [14] 0 0
FC
Country [15] 0 0
Italy
State/province [15] 0 0
MB
Country [16] 0 0
Italy
State/province [16] 0 0
MI
Country [17] 0 0
Italy
State/province [17] 0 0
Napoli
Country [18] 0 0
Spain
State/province [18] 0 0
Barcelona
Country [19] 0 0
Spain
State/province [19] 0 0
Madrid
Country [20] 0 0
Spain
State/province [20] 0 0
Valencia
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Cornwall
Country [22] 0 0
United Kingdom
State/province [22] 0 0
England
Country [23] 0 0
United Kingdom
State/province [23] 0 0
South Yorkshire
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Newcastle upon Tyne

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, open label, multicenter, safety and clinical activity study of avelumab
in combination with chemotherapy as first-line treatment of adult patients with locally
advanced or metastatic solid tumors. Initially, avelumab will be evaluated in combination
with pemetrexed and carboplatin in patients with advanced non-squamous non-small cell lung
cancer (NSCLC) (Cohort A1) and in combination with gemcitabine and cisplatin in patients with
cisplatin-eligible urothelial (bladder) cancer (UC) (Cohort A2). As more information is
learned about other anti-cancer immunotherapy agents, in future portions of the study,
avelumab may be combined with chemotherapy and other anti-cancer immunotherapy agents in
patients with these same or different tumor types.
Trial website
https://clinicaltrials.gov/show/NCT03317496
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/NCT03317496