Clinical trial NCT04246489: Bintrafusp Alfa Monotherapy in Platinum-Experienced Cervical Cancer
Official title: A Phase II, Multicenter, Open Label Study of Bintrafusp Alfa (M7824) Monotherapy in Participants With Advanced, Unresectable Cervical Cancer With Disease Progression During or After Platinum-Containing Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Uterine Cervical Neoplasms
Keywords: M7824
INTR@PID
Bintrafusp alfa
programmed death-ligand 1
Cervical Cancer
Transforming growth factor-β (TGF-β)
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2020-01-29
Enrollment: 146
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main purpose of this study was to evaluate clinical efficacy and safety of bintrafusp alfa in participants with advanced, unresectable cervical cancer with disease progression during or after platinum-containing chemotherapy.


Eligibility criteria: Inclusion Criteria:

* Participants who had advanced unresectable and/or metastatic cervical cancer (squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma) with disease progression during or after the prior platinum-containing chemotherapy:

  1. The prior platinum-containing chemotherapy may be a systemic treatment for advanced unresectable, recurrent, persistent or metastatic disease or treatment in the adjuvant or neo-adjuvant setting with disease progression or recurrence within 6 months of completion of platinum-containing chemotherapy
  2. Participants who previously only received platinum as a radiosensitizer are not eligible
  3. Participants must be naïve to checkpoint inhibitors
* Participants who had measurable disease
* Participants who provide a tumor tissue sample, either from archival tissue or newly obtained core or excisional biopsy. If the participant received local therapy (For example: radiation therapy or chemoradiotherapy) after the archival tissue was taken, a new biopsy was required
* Participants who had Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1
* Life expectancy greater than or equals to (\>=) 12 weeks as judged by the Investigator
* Adequate hematological, hepatic and renal function as defined in the protocol
* Participants with known Human Immunodeficiency Virus (HIV) infections were in general eligible if the following criteria are met:

  1. Clinically indicated participants must be stable on antiretroviral therapy (ART) for at least 4 weeks and agree to adhere to ART
  2. had no evidence of documented multi-drug resistance that would prevent effective ART
  3. had an HIV viral load of \< 400 copies per milliliter (/mL) at Screening
  4. had CD4+ T-cell (CD4+) counts \>= 350 cells/microliter
  5. For participants with a history of an Acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the last 12 months, participants may be eligible only after consultation and agreement with the study Medical Monitor
  6. If prophylactic antimicrobial drugs were indicated, participants would still be considered eligible upon agreement with the study Medical Monitor
* Participants with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections were in general eligible if the following criteria are met:

  1. HBV viral load below the limit of quantification. If medically indicated, participants infected with HBV must be treated and on a stable dose of antivirals at study entry and with planned monitoring and management according to appropriate labeling guidance
  2. Participants with a history of HCV infection should have completed curative antiviral treatment and require HCV viral load below the limit of quantification
  3. Participants on concurrent HCV treatment should have HCV below the limit of quantification
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Participants with active central nervous system (CNS) metastases causing clinical symptoms or require therapeutic intervention are excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 4 weeks, and are not using steroids for at least 7 days prior to the start of study treatment
* Participants with interstitial lung disease or has had a history of pneumonitis that has required oral or intravenous (IV) steroids
* Participants with significant acute or chronic infections
* Participants with active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
* Participants with clinically significant cardiovascular/cerebrovascular disease including: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure, or serious cardiac arrhythmia
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Number of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
timeFrame: Time from first treatment up to 688 days
Secondary outcomes:
measure: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
timeFrame: Time from first treatment up to 688 days
measure: Durable Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
timeFrame: Time from first treatment up to 688 days
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs)
timeFrame: Time from first treatment up to 688 days
measure: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)
timeFrame: Time from first administration of study drug until the first documentation of PD or death, assessed up to 688 days
measure: Number of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
timeFrame: Time from first treatment up to 688 days
measure: Overall Survival (OS)
timeFrame: Time from first administration of study drug up to data cutoff (assessed up to 688 days)
measure: Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa
timeFrame: At Day 15, Day 29, Day 43, Day 85, Day 127, Day 169, Day 253, Day 337, Day 421, Day 505 and Day 589
measure: Serum Concentration at End of Infusion (CEOI) of Bintrafusp Alfa
timeFrame: At Day 1 and Day 29
measure: Number of Participants With Positive Antidrug Antibodies (ADA)
timeFrame: Time from first treatment up to 688 days
measure: Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression
timeFrame: Time from first treatment up to 688 days
measure: PFS According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression
timeFrame: Time from first administration of study drug until the first documentation of PD or death, assessed up to 688 days
measure: Overall Survival (OS) as Assessed According to Programmed Death Ligand 1 (PD-L1) Expression
timeFrame: Time from first administration of study drug up to 688 days
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas Medical Sciences
state: Arkansas
city: Stanford
country: United States
facility: Stanford University Hospital and Clinics - Stanford Cancer Center
state: California
city: Stamford
country: United States
facility: The Stamford Hospital
state: Connecticut
city: Farmington Hills
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Cincinnati
country: United States
facility: UC Health Clinical Trials Office
state: Ohio
city: Portland
country: United States
facility: Oregon Health &amp; Science University
state: Oregon
city: Germantown
country: United States
facility: The West Clinic
state: Tennessee
city: Nashville
country: United States
facility: SCRI - Tennessee Oncology
state: Tennessee
city: La Rioja
country: Argentina
facility: Centro Oncologico Riojano Integral (CORI)
city: Salta
country: Argentina
facility: Sanatorio El Parque
city: San Miguel de Tucuman
country: Argentina
facility: Centro Medico San Roque S.R.L.
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre-East Melbourne
city: Nedlands
country: Australia
facility: Linear Clinical Research Limited
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Bruxelles
country: Belgium
facility: Institut Jules Bordet
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent - Pneumology
city: Kortrijk
country: Belgium
facility: AZ Groeninge - Campus Kennedylaan - account 2
city: Liège
country: Belgium
facility: CHU de Liège - PARENT
city: Liège
country: Belgium
facility: CHU Sart Tilman
city: Pellenberg
country: Belgium
facility: UZ Leuven
city: Wilrijk
country: Belgium
facility: GZA Ziekenhuizen - Campus Sint-Augustinus
city: Porto Alegre
country: Brazil
facility: HGB - Hospital Giovanni Battista - Mãe de Deus Center - Centro de Pesquisa Clínica - Instituto do Câncer
city: São Paulo
country: Brazil
facility: Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda.
city: São Paulo
country: Brazil
facility: IBCC - Instituto Brasileiro de Controle do Câncer
city: Chongqing
country: China
facility: Chongqing Cancer Hospital
city: Guangzhou
country: China
facility: Sun Yat-sen University, Cancer Center
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Shanghai
country: China
facility: Shanghai Cancer Hospital, Fudan University
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Bordeaux cedex
country: France
facility: Institut Bergonié
city: Lille cedex
country: France
facility: Centre Oscar lambret - Service d'Oncologie medicale
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hôpital Cochin - Hematologie et Oncologie Médicale
city: Pierre Benite cedex
country: France
facility: Centre Hospitalier Lyon Sud - service d'oncologie medicale
city: Plérin
country: France
facility: CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie
city: Reims cedex
country: France
facility: Institut Jean Godinot - Service d'hématologie et Oncologie Médicale
city: Saint Herblain
country: France
facility: ICO - Site René Gauducheau
city: Strasbourg
country: France
facility: Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet - Nogyogyaszati Osztaly
city: Nyiregyhaza
country: Hungary
facility: SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz - Onkoradiologia
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital - Dept of Mammary Gland/Oncology
city: Fukuoka-shi
country: Japan
facility: NHO Kyushu Cancer Center - Dept of Gynecology
city: Hidaka-shi
country: Japan
facility: Saitama Medical University International Medical Center - Dept of Gynecology/Oncology
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of JFCR - Dept of Gynecology
city: Kurume-shi
country: Japan
facility: Kurume University Hospital - Dept of Gynecology
city: Minato-ku
country: Japan
facility: Jikei University Hospital - Dept of Gynecology
city: Nakagami-gun
country: Japan
facility: University Hospital, University of the Ryukyus - Dept of Obstetrics/Gynecology
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute - Dept of Gynecology
city: Sapporo-shi
country: Japan
facility: NHO Hokkaido Cancer Center - Dept of Gynecology
city: Yokohama-shi
country: Japan
facility: Kanagawa Cancer Center - Dept of Gynecology
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Suwon
country: Korea, Republic of
facility: Ajou University Hospital
city: Omsk
country: Russian Federation
facility: BHI of Omsk region "Clinical Oncology Dispensary"
city: Pyatigorsk
country: Russian Federation
facility: LLC "ClinicaUZI4D"
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron - Dept of Oncology
city: Girona
country: Spain
facility: ICO Girona - Hospital Doctor Josep Trueta - Servicio de Oncologia Medica
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra (MAD) - Oncology Service
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre - Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal - Servicio de Oncologia
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Strauss J, Heery CR, Schlom J, Madan RA, Cao L, Kang Z, Lamping E, Marte JL, Donahue RN, Grenga I, Cordes L, Christensen O, Mahnke L, Helwig C, Gulley JL. Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFbeta, in Advanced Solid Tumors. Clin Cancer Res. 2018 Mar 15;24(6):1287-1295. doi: 10.1158/1078-0432.CCR-17-2653. Epub 2018 Jan 3.
citation: Lan Y, Zhang D, Xu C, Hance KW, Marelli B, Qi J, Yu H, Qin G, Sircar A, Hernandez VM, Jenkins MH, Fontana RE, Deshpande A, Locke G, Sabzevari H, Radvanyi L, Lo KM. Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein simultaneously targeting PD-L1 and TGF-beta. Sci Transl Med. 2018 Jan 17;10(424):eaan5488. doi: 10.1126/scitranslmed.aan5488.
citation: Vugmeyster Y, Grisic AM, Wilkins JJ, Loos AH, Hallwachs R, Osada M, Venkatakrishnan K, Khandelwal A. Model-informed approach for risk management of bleeding toxicities for bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1. Cancer Chemother Pharmacol. 2022 Oct;90(4):369-379. doi: 10.1007/s00280-022-04468-6. Epub 2022 Sep 6.