Safety And Efficacy Study Of Avelumab Plus Chemotherapy With Or Without Other Anti-Cancer Immunotherapy Agents In Patients With Advanced Malignancies

NCT03317496 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: B99910232017-001741-27JAVELIN CHEMOTHERAPY MEDLEY
• Study Type: interventional
• Target: 67
• Locations: 8 countries
• Sites: 46

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.

Conditions

Non-small Cell Lung Cancer; Urothelial Cancer

Keywords

Avelumab, immunotherapy, PD-L1 inhibitor, non-small cell lung cancer (NSCLC), urothelial cancer (UC), carboplatin, pemetrexed, gemcitabine, cisplatin

Outcome Measures

Primary Outcomes (2)

• Phase 1b Lead-in: Number of Participants With Dose-Limiting Toxicities (DLT)

  DLTs=occurrence of any AEs attributable to study treatment in first 2 treatment cycles:Hematologic: grade(G)4 neutropenia lasting \>7days;febrile neutropenia with body temperature \>=38 degree Celsius for \>1hour; G\>=3 neutropenic infection(absolute neutrophil count \<1.0\*10\^9/L),G\>=3 thrombocytopenia (platelet count\<50.0-25.0\*10\^9/L)with bleeding;G4 thrombocytopenia(PC\<25.0\*10\^9/L),G4 anemia(life-threatening).Non-hematologic: any G4 toxicities;G3 toxicities persisting for \>3days despite medical treatment(nausea,vomiting,diarrhea)except endocrinopathies controlled with hormonal therapy;ALT/AST \>3\*upper limit of normal(ULN)if normal at baseline or 2\*Baseline(\>ULN at baseline)with total bilirubin \>2\*ULN and alkaline phosphatase \<2\*ULN;G3 QTcF prolongation after correction of any reversible cause(electrolyte abnormalities/hypoxia).Delay of \>=3weeks in scheduled administration/failure to deliver 75% of doses due to toxicities attributable to any study treatment. DLT-evaluable analysis set.

  Day 1 up to Week 6 (first 2 treatment cycles; 1 cycle = 21 days)

• Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment

  OR: complete response(CR) or partial response(PR)determined by investigator according to RECIST v1.1 from date of first dose of study treatment until date of first documentation of progressive disease(PD),confirmed by repeat assessments performed no less than 4 weeks after first response. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (\<)10 millimeter(mm). PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD.

  From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 3.5 years approximately)

Secondary Outcomes (12)

• Serum Concentration of Avelumab

  Pre-dose, 1 hour post-dose on Day 1 of Cycle 1, 2, 3, 6, 10, 14; 336 hours post-dose on Day 15 of Cycle 1, 2, 3 (each cycle of 21 days)

• Absolute Value of Tumor Mutational Burden (TMB) in Tumor Tissue

  Pre-dose on Day 1 of Cycle 1

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

  From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5 years approximately)

• Number of Participants With Treatment Related TEAEs

  From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5 years approximately)

• Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03

  From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5 years approximately)

Study Arms (4)

Group A Cohort A1

EXPERIMENTAL

Non-squamous non-small cell lung cancer (NSCLC) patients treated with 800 mg avelumab plus pemetrexed/carboplatin

Drug: Avelumab 800 mg in combination with pemetrexed / carboplatin

Group A Cohort A2

EXPERIMENTAL

Cisplatin-eligible urothelial cancer (UC)patients treated with 800 mg avelumab plus gemcitabine/cisplatin

Drug: Avelumab 800 mg in combination with gemcitabine / cisplatin.

Group A Cohort A3

EXPERIMENTAL

Non-squamous non-small cell lung cancer (NSCLC) patients treated with 1200 mg avelumab plus pemetrexed/carboplatin

Drug: Avelumab 1200 mg in combination with pemetrexed/carboplatin

Group A Cohort A4

EXPERIMENTAL

Cisplatin-eligible urothelial cancer (UC) patients treated with 1200 mg avelumab plus gemcitabine/cisplatin

Drug: Avelumab 1200 mg in combination with gemcitabine/cisplatin

Interventions

Avelumab 800 mg in combination with pemetrexed / carboplatin DRUG

Avelumab Pemetrexed Carboplatin

Group A Cohort A1

Avelumab 800 mg in combination with gemcitabine / cisplatin. DRUG

Avelumab Gemcitabine Cisplatin

Group A Cohort A2

Avelumab 1200 mg in combination with pemetrexed/carboplatin DRUG

Avelumab Pemetrexed Carboplatin

Group A Cohort A3

Avelumab 1200 mg in combination with gemcitabine/cisplatin DRUG

Avelumab Gemcitabine Cisplatin

Group A Cohort A4

Eligibility Criteria

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

You may qualify if:

• 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.
• ECOG performance status 0 or 1
• Estimated life expectancy of at least 90 days
• Adequate bone marrow, renal, and liver function
• Negative serum pregnancy test at screening
• Signed and dated informed consent

You may not qualify if:

• Prior immunotherapy with any antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
• Patients with known symptomatic central nervous system metastases requiring steroids.
• 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
• Use of immunosuppressive medication at the time of enrollment
• Active or prior autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent.
• Prior organ transplantation including allogenic stem cell transplantation
• Active infection requiring systemic therapy
• Known history of HIV or AIDS
• Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening
• Administration of live vaccine within 4 weeks prior to study entry
• Known prior severe hypersensitivity to the investigational products or any component in their formulations,
• 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
• Persisting toxicity related to prior therapy (NCI CTCAE v4.03 Grade \> 1)
• Known history of colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis.
• Ongoing cardiac dysrhythmias of NCI CTCAE v4.03 Grade 2 or prolongation of the QTcF interval to \>480 msec.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (46)

University of Arizona Cancer Center - North Campus

Tucson, Arizona, 85719, United States

Location

Banner-University Medical Center Tucson

Tucson, Arizona, 85724, United States

Location

Stony Brook Cancer Center

Stony Brook, New York, 11794, United States

Location

Stony Brook University

Stony Brook, New York, 11794, United States

Location

Montefiore Medical Center - Einstein Center for Cancer Care

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center - Moses Division

The Bronx, New York, 10467, United States

Location

Duke University Medical Center/Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Investigational Chemotherapy Service

Durham, North Carolina, 27710, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

St Vincent's Public Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Western Health, Sunshine Hospital

St Albans, Victoria, 3021, Australia

Location

Kingston Health Sciences Centre -

Kingston, Ontario, K7L 2V7, Canada

Location

Fakultni nemocnice Olomouc, Klinika nuklearni mediciny

Olomouc, 779 00, Czechia

Location

Fakultni nemocnice Olomouc, Ustav klinicke a molekularni patologie

Olomouc, 779 00, Czechia

Location

Fakultni nemocnice Olomouc

Olomouc, 779 00, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 120 00, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 00, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 08, Czechia

Location

Vseobecna fakultni nemocnice v Praze

Prague, 128 21, Czechia

Location

Thomayerova nemocnice

Prague, 140 59, Czechia

Location

Thomayerova nemocnice

Prague, 14059, Czechia

Location

Centrum nuklearni mediciny s.r.o.

Prague, 180 81, Czechia

Location

Centrum nuklearni mediciny s.r.o.

Prague, 190 61, Czechia

Location

Orszagos Onkologiai Intezet "C" Belgyogyaszati - Onkologiai es Klinikai Farmakologiai Osztaly

Budapest, 1122, Hungary

Location

AOU Ospedali Riuniti di Ancona Umberto I - GM Lancisi - G Salesi

Torrette Di Ancona, AN, 60126, Italy

Location

IRCCS Istit.Scient.Romagnolo per lo Studio e la Cura dei Tumori

Meldola, FC, 47014, Italy

Location

Centro di Ricerca di Fase 1, ASST Monza-Ospedale San Gerardo

Monza, MB, 20900, Italy

Location

Oncologia, ASST Monza-Ospedale San Gerardo

Monza, MB, 20900, Italy

Location

Istituto Europeo di Oncologia (IEO)

Milan, MI, 20141, Italy

Location

Istituto Nazionale Tumori di Napoli IRCCS Fondazione Pascale

Napoli, 80131, Italy

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic I Provincial

Barcelona, 08036, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Fundacion Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Royal Cornwall Hospital

Truro, Cornwall, TR1 3LJ, United Kingdom

Location

The Platinum Medical Centre

London, England, NW8 7JA, United Kingdom

Location

The Wellington Hospital - South

London, England, NW8 9LE, United Kingdom

Location

Sarah Cannon Research Institute UK

London, England, W1G 6AD, United Kingdom

Location

The Harley Street Clinic

London, England, W1G 7LJ, United Kingdom

Location

HCA Pharmacy Department

London, England, W1G 8HL, United Kingdom

Location

The Harley Street Clinic

London, England, W1G 8PP, United Kingdom

Location

The Princess Grace Hospital

London, England, W1U 5LZ, United Kingdom

Location

Weston Park Hospital

Sheffield, South Yorkshire, S10 2SJ, United Kingdom

Location

Sir Bobby Robson Cancer Trials Research Centre

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (1)

• Wheatley DA, Berardi R, Climent Duran MA, Tomiak A, Greystoke AP, Joshua AM, Arkenau HT, Geczi L, Corbacho JG, Paz-Ares LG, Hussain SA, Petruzelka L, Delmonte A, Chappey C, Masters JC, Michelon E, Murphy DA, Mwewa S, Cesari R, Doger de Speville B. First-line Avelumab plus Chemotherapy in Patients with Advanced Solid Tumors: Results from the Phase Ib/II JAVELIN Chemotherapy Medley Study. Cancer Res Commun. 2024 Jun 28;4(6):1609-1619. doi: 10.1158/2767-9764.CRC-23-0459.

  PMID: 38669053 DERIVED

Related Links

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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

avelumab; Pemetrexed; Carboplatin; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Limitations and Caveats

The study was terminated since there was no need for further safety or efficacy data to be collected. The subjects having benefit from the investigational treatments have been moved to a continuation study NCT05059522

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

8007181021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: October 23, 2017
• Study Start: December 21, 2017
• Primary Completion: June 7, 2021
• Study Completion: December 20, 2022
• Last Updated: August 29, 2023
• Results First Posted: June 23, 2022

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

ES (5); AU (4); CA (1); CZ (11); HU (1); IT (6); US (8); GB (10)