MSB0011359C (M7824) in Metastatic or Locally Advanced Solid Tumors

Study at a glance

From the registry record, last updated by the sponsor on 3 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, PK, Biological and Clinical Activity of MSB0011359C in Subjects With Metastatic or Locally Advanced Solid Tumors and Expansion to Selected Indications

ClinicalTrials.gov ID

NCT02517398

Acronym / sponsor ID

EMR 200647-001

Conditions

Solid Tumors

Keywords

Solid tumor, MSB0011359C (M7824), Metastatic or Locally Advanced Solid Tumors, Bintrafusp alfa, INTR@PID

Phase

Phase 1

Study type

Interventional

Recruitment status

Completed

Enrolment

600 participants (actual)

Lead sponsor

EMD Serono Research & Development Institute, Inc.Industry (pharma, biotech, devices)

Collaborators

Merck KGaA, Darmstadt, Germany

Study start

31 Aug 2015 (actual)

Primary completion

23 May 2022 (actual)

Study completion

23 May 2022 (actual)

First posted

7 Aug 2015 (estimated)

Results

Posted 3 May 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Not applicable

Intervention model

Single group

Masking

None (open label)

Number of arms

1

Who may qualify

Ages

18 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Dose-escalation: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

   Time frame: From start of study drug administration up to 139 weeks

   Adverse event (AE): any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs.

2. Dose-escalation: Number of Participants With Treatment-Related TEAEs, Treatment-Related Serious TEAEs and Treatment-related TEAEs Leading to Death

   Time frame: From start of study drug administration up to 139 weeks

   Treatment-related TEAEs are any untoward medical occurrence in a participant who received study drug with causal relationship with the investigational product as assessed by the investigator. Related TEAEs were events with relationship missing, unknown or yes. Number of participants With treatment-related TEAEs, treatment-related serious TEAEs and treatment-related TEAE leading to death were reported.

3. Number of Participants With TEAEs and Related TEAEs Based on Severity According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03

   Time frame: From start of study drug administration up to 139 weeks

   AEs were graded according to severity using NCI-CTCAE Version 4.03. Severity of TEAEs were graded as Grade 1: mild (not causing any significant problem, dose adjustment not required), Grade 2: moderate (caused problem that does not interfere significantly with usual activities or the clinical status, dose adjustment needed due to adverse event), Grade 3: Severe (caused problem that interferes significantly with usual activities or the clinical status, study drug stopped due to adverse event), Grade 4: Life-threatening, Grade 5: Death. Number of Participants with TEAEs and Related TEAEs Based on Severity having Grade greater than or equal to (>=) 3 and Grade >=4 were reported.

4. Dose-escalation: Number of Participants With Dose-Limiting Toxicities According to the National Cancer Institute Common Terminology Criteria For Adverse Events(NCI-CTCAE), v4.03

   Time frame: From start of study drug administration up to 21 days

   A DLT was defined as any grade >= 3 Adverse Event (AE) suspected to be related to IMP by the Investigator and / or Sponsor occurring in the DLT evaluation period confirmed by the Safety Monitoring Committee (SMC) to be relevant for the IMP treatment. According to the NCI-CTCAE, v4.03, occurring in the DLT evaluation period and assessed to be related to study treatment by the Investigator and / or Sponsor confirmed by the safety monitoring committee to be relevant for the study treatment.

5. Dose-expansion: Number of Participants With Best Overall Response (BOR) as Assessed by Independent Endpoint Review Committee (IRC)

   Time frame: From date of randomization up to Week 66

   BOR according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and as adjudicated by the Independent Endpoint Review Committee (IRC). BOR is defined as sum of complete response and partial response (CR+PR). For target lesions (TLs), CR was defined as the disappearance of all TLs; PR was defined as at least a 30% decrease in the sum of largest diameter (SLD) of the TLs, taking as a reference the baseline SLD.

6. Dose-expansion: Disease Control Rate According to Response Assessment in Neuro-Oncology (RANO) as Adjudicated by the IRC for Participants With Glioblastoma

   Time frame: From date of randomization up to Week 66

   DCR is defined as the percentage of participants with a confirmed CR+PR+SD+ Non-CR/non-PD at any time as per RANO criteria. A responder is a participant with a Complete Response (CR) or Partial Response (PR), and a non-responder is a participant with Stable Disease (SD) or Progressive Disease (PD) assessed by the RANO criteria. CR is no T1 gadolinium enhancing disease, no new lesions, or corticosteroids, and stable or decreasing T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR). PR is ≥50% decrease in T1 gadolinium enhancing disease, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increasing clinical status. SD is <50% decrease in T1 gadolinium enhancing disease but < 25% increase, no new lesions, stable or decreasing T2/FLAIR or corticosteroids, and stable or increase in clinical status. PD is ≥25% increase in T1 gadolinium enhancing disease.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2024.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Results publication: PubMed 33323462Strauss J, Gatti-Mays ME, Cho BC, Hill A, Salas S, McClay E, Redman JM, Sater HA, Donahue RN, Jochems C, Lamping E, Burmeister A, Marte JL, Cordes LM, Bilusic M, Karzai F, Ojalvo LS, Jehl G, Rolfe PA, Hinrichs CS, Madan RA, Schlom J, Gulley JL. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with human papillomavirus-associated malignancies. J Immunother Cancer. 2020 Dec;8(2):e001395. doi: 10.1136/jitc-2020-001395.
• Results publication: PubMed 32641320Cho BC, Daste A, Ravaud A, Salas S, Isambert N, McClay E, Awada A, Borel C, Ojalvo LS, Helwig C, Rolfe PA, Gulley JL, Penel N. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in advanced squamous cell carcinoma of the head and neck: results from a phase I cohort. J Immunother Cancer. 2020 Jul;8(2):e000664. doi: 10.1136/jitc-2020-000664.
• Results publication: PubMed 31278692Wilkins JJ, Vugmeyster Y, Dussault I, Girard P, Khandelwal A. Population Pharmacokinetic Analysis of Bintrafusp Alfa in Different Cancer Types. Adv Ther. 2019 Sep;36(9):2414-2433. doi: 10.1007/s12325-019-01018-0. Epub 2019 Jul 5.
• Results publication: PubMed 29298798Strauss 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.
• Results publication: PubMed 34009501Tan B, Khattak A, Felip E, Kelly K, Rich P, Wang D, Helwig C, Dussault I, Ojalvo LS, Isambert N. Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-beta and PD-L1, in Patients with Esophageal Adenocarcinoma: Results from a Phase 1 Cohort. Target Oncol. 2021 Jul;16(4):435-446. doi: 10.1007/s11523-021-00809-2. Epub 2021 May 19.
• Derived from this study: PubMed 39141577Lim HY, Heo J, Peguero JA, Ryoo BY, Decaens T, Barlesi F, Moehler MH, Jehl G, Eggleton SP, Bajars M, Gulley JL. Efficacy and safety of bintrafusp alfa in 2 phase I expansion cohorts with advanced HCC. Hepatology. 2025 Jan 1;81(1):32-43. doi: 10.1097/HEP.0000000000001054. Epub 2024 Aug 13.
• Derived from this study: PubMed 38485188Rajan A, Abdul Sater H, Rahma O, Agajanian R, Lassoued W, Marte JL, Tsai YT, Donahue RN, Lamping E, Bailey S, Weisman A, Walter-Rodriguez B, Ito R, Vugmeyster Y, Sato M, Machl A, Schlom J, Gulley JL. Efficacy, safety, and biomarker analyses of bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1, in patients with advanced non-small cell lung cancer. J Immunother Cancer. 2024 Mar 13;12(3):e008480. doi: 10.1136/jitc-2023-008480.
• Derived from this study: PubMed 36568239Spira A, Awada A, Isambert N, Lorente D, Penel N, Zhang Y, Ojalvo LS, Hicking C, Rolfe PA, Ihling C, Dussault I, Locke G, Borel C. Identification of HMGA2 as a predictive biomarker of response to bintrafusp alfa in a phase 1 trial in patients with advanced triple-negative breast cancer. Front Oncol. 2022 Dec 8;12:981940. doi: 10.3389/fonc.2022.981940. eCollection 2022.
• Derived from this study: PubMed 36066618Vugmeyster 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.
• Trial Awareness and Transparency websiteLink provided by the sponsor.
• US Medical Information website, Medical ResourcesLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

118 sites in 12 countries: see every site and its status.