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BRIEF TITLE: 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

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


  • Org Study ID: B9991023
  • Secondary ID: B9991023,2017-001741-27,JAVELIN CHEMOTHERAPY MEDLEY
  • NCT ID: NCT03317496
  • NCT Alias:
  • Sponsor: Pfizer - Industry
  • Source: Pfizer

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.

Detailed Description


This is a Phase 1b/2, open label, multicenter, safety, clinical activity, pharmacokinetic
(PK), and pharmacodynamics (PD) study of avelumab in combination with chemotherapy with or
without other anti-cancer immunotherapies, 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 with gemcitabine and cisplatin in patients with
cisplatin-eligible urothelial cancer (UC) (Cohort A2).

Given the growing preclinical and clinical indications that combinations of anti-cancer
immunotherapies potentially improve patient outcomes compared to results seen with single
agents, in portions of the study to be added in the future, avelumab will be evaluated in
combination with both standard-of-care chemotherapy and other anti-cancer immunotherapies in
patients with advanced malignancies. Each cohort in the study will consist of a Phase 1b
lead-in portion to evaluate safety and a Phase 2 cohort expansion to evaluate safety and
efficacy.

In the Phase 1b safety lead-in portion, up to 12 patients will be enrolled into each cohort
and evaluated for dose-limiting toxicities (DLT) during the first 2 cycles of treatment. If
investigational products administration in a cohort is deemed safe in the Phase 1b lead-in,
enrollment may be expanded into the Phase 2 cohort expansion. Up to approximately 40 patients
in each cohort (including those enrolled in the Phase 1b lead-in and those enrolled in the
Phase 2 cohort expansion) will be enrolled and treated with avelumab plus chemotherapy in the
initial portion of the study and, in future portions of the study, with avelumab plus
chemotherapy with or without other anti-cancer immunotherapies.

In the Phase 1b lead-in portions of NSCLC Cohort A1 and UC Cohort A2, avelumab is dosed at
800 mg fixed dose every 3 weeks. Under Protocol Amendment 4, avelumab is dosed at 1200 mg
fixed dose every 3 weeks in the Phase 1b lead-in portions of NSCLC Cohort A3 and in UC Cohort
A4, in combination with the same standard-of-care chemotherapy doublets used in Cohort A1 and
Cohort A2, respectively. For each tumor type, the study treatment combination with the
highest avelumab dose determined to be safe may be advanced into Phase 2 cohort expansion.

Overal Status Start Date Phase Study Type
Recruiting December 21, 2017 Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Phase 1b lead-in: Number of patients with dose-limiting toxicities in first 2 cycles

Primary Outcome 1 - Time Frame: First 6 weeks of treatment

Primary Outcome 2 - Measure: Confirmed objective response (OR)

Primary Outcome 2 - Time Frame: Baseline up to approximately 24 months

Condition:

  • Non-small Cell Lung Cancer
  • Urothelial Cancer

Eligibility

Criteria:
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

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.
Show More

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Pfizer CT.gov Call Center

Role: Study Director

Affiliation: Pfizer

Overall Contact

Name: Pfizer CT.gov Call Center

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Link: To obtain contact information for a study center near you, click here.

Locations

Facility Status Contact
University of Arizona Cancer Center - North Campus
Tucson, Arizona 85719
United States
Terminated
Banner-University Medical Center Tucson
Tucson, Arizona 85724
United States
Terminated
Keck Hospital of USC - Norris Healthcare Center (HC3)
Los Angeles, California 90033
United States
Recruiting
Keck Hospital of USC
Los Angeles, California 90033
United States
Recruiting
LAC+USC Medical Center
Los Angeles, California 90033
United States
Recruiting
USC/Norris Comprehensive Cancer Center
Los Angeles, California 90033
United States
Recruiting
Hoag Memorial Hospital Presbyterian
Newport Beach, California 92663
United States
Recruiting
Montefiore Medical Center - Einstein Center for Cancer Care
Bronx, New York 10461
United States
Recruiting
Montefiore Medical Center - Moses Division
Bronx, New York 10467
United States
Recruiting
Roswell Park Cancer Institute
Buffalo, New York 14263
United States
Recruiting
Stony Brook Cancer Center
Stony Brook, New York 11794
United States
Terminated
Stony Brook University
Stony Brook, New York 11794
United States
Terminated
Duke University Medical Center/Duke Cancer Center
Durham, North Carolina 27710
United States
Terminated
Investigational Chemotherapy Service
Durham, North Carolina 27710
United States
Terminated
Chris O'Brien Lifehouse
Camperdown, New South Wales 2050
Australia
Recruiting
St Vincent's Public Hospital Sydney
Darlinghurst, New South Wales 2010
Australia
Recruiting
Sunshine Coast University Hospital
Birtinya, Queensland 4575
Australia
Not yet recruiting
Slade Health Pharmacy
Geebung, Queensland 4034
Australia
Not yet recruiting
Cancer Melbourne
Richmond, Victoria 3121
Australia
Not yet recruiting
Epworth Healthcare - Epworth Richmond
Richmond, Victoria 3121
Australia
Not yet recruiting
Western Health, Sunshine Hospital
St Albans, Victoria 3021
Australia
Recruiting
Kingston Health Sciences Centre -
Kingston, Ontario K7L 2V7
Canada
Recruiting
Princess Margaret Cancer Centre
Toronto, Ontario M5G 2M9
Canada
Not yet recruiting
Vseobecna fakultni nemocnice v Praze, Fakultni poliklinika
Praha 2, Czech Republic 128 08
Czechia
Recruiting
Fakultni nemocnice Olomouc, Klinika nuklearni mediciny
Olomouc, 779 00
Czechia
Recruiting
Fakultni nemocnice Olomouc, Oddeleni magneticke rezonance (MR)
Olomouc, 779 00
Czechia
Recruiting
Fakultni nemocnice Olomouc, Oddeleni vypocetni tomografie (CT)
Olomouc, 779 00
Czechia
Recruiting
Fakultni nemocnice Olomouc, Ustav klinicke a molekularni patologie
Olomouc, 779 00
Czechia
Recruiting
Fakultni nemocnice Olomouc
Olomouc, 779 00
Czechia
Recruiting
Thomayerova nemocnice
Prague, 140 59
Czechia
Not yet recruiting
Centrum nuklearni mediciny s.r.o.
Prague, 180 81
Czechia
Not yet recruiting
Nemocnice na Bulovce
Prague, 18081
Czechia
Not yet recruiting
Centrum nuklearni mediciny s.r.o.
Prague, 190 61
Czechia
Not yet recruiting
Vseobecna fakultni nemocnice v Praze
Praha 2, 120 00
Czechia
Recruiting
Vseobecna fakultni nemocnice v Praze
Praha 2, 128 00
Czechia
Recruiting
Vseobecna fakultni nemocnice v Praze
Praha 2, 128 08
Czechia
Recruiting
Vseobecna fakultni nemocnice v Praze
Praha 2, 128 21
Czechia
Recruiting
Thomayerova nemocnice
Praha 4, 14059
Czechia
Not yet recruiting
Fakultni nemocnice v Motole, Onkologicka klinika
Praha 5, 150 06
Czechia
Not yet recruiting
Fakultni nemocnice v Motole
Praha 5, 150 06
Czechia
Not yet recruiting
Centrum nuklearni mediciny s.r.o.
Praha 8, 180 81
Czechia
Not yet recruiting
Nemocnice Na Bulovce
Praha 8, 180 81
Czechia
Not yet recruiting
Orszagos Onkologiai Intezet "C" Belgyogyaszati - Onkologiai es Klinikai Farmakologiai Osztaly
Budapest, 1122
Hungary
Recruiting
AOU Ospedali Riuniti di Ancona Umberto I - GM Lancisi - G Salesi
Torrette Di Ancona, AN 60126
Italy
Recruiting
IRCCS Istit.Scient.Romagnolo per lo Studio e la Cura dei Tumori
Meldola, FC 47014
Italy
Recruiting
Centro di Ricerca di Fase 1, ASST Monza-Ospedale San Gerardo
Monza, MB 20900
Italy
Recruiting
Oncologia, ASST Monza-Ospedale San Gerardo
Monza, MB 20900
Italy
Recruiting
Istituto Europeo di Oncologia (IEO)
Milano, MI 20141
Italy
Not yet recruiting
Istituto Nazionale Tumori di Napoli IRCCS Fondazione Pascale
Napoli, 80131
Italy
Not yet recruiting
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Spain
Recruiting
Hospital Clinic I Provincial
Barcelona, 08036
Spain
Recruiting
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040
Spain
Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
Spain
Recruiting
Fundacion Instituto Valenciano de Oncologia
Valencia, 46009
Spain
Recruiting
Royal Cornwall Hospital
Truro, Cornwall TR1 3LJ
United Kingdom
Recruiting
The Platinum Medical Centre
London, England NW8 7JA
United Kingdom
Not yet recruiting
The Wellington Hospital - South
London, England NW8 9LE
United Kingdom
Not yet recruiting
Sarah Cannon Research Institute UK
London, England W1G 6AD
United Kingdom
Not yet recruiting
The Harley Street Clinic
London, England W1G 7LJ
United Kingdom
Not yet recruiting
HCA Pharmacy
London, England W1G 8HL
United Kingdom
Not yet recruiting
The Harley Street Clinic
London, England W1G 8PP
United Kingdom
Not yet recruiting
The Princess Grace
London, England W1U 5LZ
United Kingdom
Not yet recruiting
Weston Park Hospital
Sheffield, South Yorkshire S10 2SJ
United Kingdom
Recruiting
Sir Bobby Robson Cancer Trials Research Centre
Newcastle upon Tyne, NE7 7DN
United Kingdom
Recruiting