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JOURNAL ONKOLOGIE – STUDIE

First in Human Study of M6223

Rekrutierend

NCT-Nummer:
NCT04457778

Studienbeginn:
Juli 2020

Letztes Update:
10.06.2021

Wirkstoff:
M6223, Bintrafusp alfa

Indikation (Clinical Trials):
Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
EMD Serono Research & Development Institute, Inc.

Collaborator:
Merck KGaA, Darmstadt, Germany

Studienleiter

Medical Responsible
Study Director
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Kontakt

Studienlocations
(3 von 4)

Alle anzeigen

Studien-Informationen

Brief Summary:

The main purpose of this study is to determine the safety, tolerability, pharmacokinetics

(PK), immunogenicity and (if observed) the maximum tolerated dose (MTD) of M6223 as a single

agent (Part 1A) and of M6223 combined with bintrafusp alfa [Part 1B, for both the every 2

weeks (Q2W) regimen and the every 3 weeks (Q3W) regimen] in participants with metastatic or

locally advanced solid unresectable tumors.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Participants have histologically or cytologically proven locally advanced or advanced

solid malignancies who are refractory to or have progressed under standard treatment

and have no other treatment options known to confer clinical benefit

- Participants with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0

to 1 at Screening

- Participant has a formalin-fixed paraffin-embedded block containing tumor tissue or a

minimum of 15 (preferably 25) unstained tumor slides suitable for

immunohistochemistry-based staining of protein expression

- Participants with life expectancy of at least 12 weeks

- Participants with measurable disease according to Response Evaluation Criteria in

Solid Tumors version 1.1 (RECIST 1.1)

- Adequate hematological, hepatic and renal function as defined in the protocol

- Other protocol defined inclusion criteria may apply

Exclusion Criteria:

- Participants with persisting toxicity related to prior therapy Grade greater than (>)

1 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE)

Version 5.0, however, alopecia, sensory neuropathy Grade less than or equal to (<=) 2,

or other non-immune-related Grade <= 2 not constituting a safety risk

- Participants with prior organ transplantation including allogeneic stem cell

transplantation

- Participants with prior toxicity related to an immune checkpoint inhibitor Grade

greater than equal to (>=) 3 NCI-CTCAE Version 5.0 unless resolved to Grade <= 1 prior

to study inclusion

- Participants with current significant cardiac conduction abnormalities, including

corrected QT interval (QTcF, corrected with Fridericia formula) prolongation of > 450

milli seconds (ms) on triplicate 12-lead ECG or impaired cardiovascular function,

ventricular tachycardia, hypokalemia or a history of paroxysmal atrial fibrillation,

serious cardiac arrhythmia and family history of sudden death or long QT syndrome

- A history of vascular, cardiovascular or cerebrovascular disease like, cerebral

vascular accident/stroke (less than [<] 6 months prior to enrollment), myocardial

infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure

(New York Heart Association Classification Class >= II), deep vein thrombosis (< 3

months prior to enrollment) or pulmonary thrombosis/embolism (< 3 months prior to

enrollment)

- Other protocol defined exclusion criteria may apply

Studien-Rationale

Primary outcome:

1. Part 1A and 1B: Occurrence of Dose Limiting Toxicities (DLTs) During the DLT Observation Period (28 Days) (Time Frame - Day 1 to Day 28)

2. Part IA and IB: Occurrence of Treatment-Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events (TRAEs) According to the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) version 5 (Time Frame - Time from first study drug administration to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years))

3. Part IA and IB: Occurrence of Treatment-Emergent Adverse Events (TEAEs) as per Severity and Deaths (Time Frame - Time from first study drug administration to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years))

4. Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Clinical Laboratory Measures (Time Frame - Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years))

5. Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Electrocardiogram Findings (Time Frame - Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years))

6. Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Vital Signs (Time Frame - Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years))

7. Part IA and IB: Occurrence of Change From Baseline in Eastern Cooperative Oncology Group Performance Status (Time Frame - Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years))

Secondary outcome:

1. Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M6223 (Time Frame - Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen))

2. Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC 0-inf) of M6223 (Time Frame - Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen))

3. Part 1A and Part 1B: Area Under Serum Concentration-Time Curve Over a Dosing Interval From Time Zero to Tau (τ) (AUCτ) of M6223 (Time Frame - Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen))

4. Part 1A and Part 1B: Maximum Observed Serum Concentration (Cmax) of M6223 (Time Frame - Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen))

5. Part 1A and Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of M6223 (Time Frame - Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen))

6. Part 1A and Part 1B: Time to Reach Maximum Serum Concentration (Tmax) of M6223 (Time Frame - Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen))

7. Part 1A and Part 1B: Apparent Terminal Half-Life (t1/2) of M6223 (Time Frame - Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen))

8. Part 1A and Part 1B: Elimination Rate Constant (Lambda z) of M6223 (Time Frame - Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen))

9. Part 1B: Maximum Observed Serum Concentration (Cmax) of Bintrafusp alfa (Time Frame - Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen))

10. Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Bintrafusp alfa (Time Frame - Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen))

11. Part IA and 1B: Immunogenicity of M6223 Measured by Antidrug Antibody (ADA) Assays (Time Frame - Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen) up to end of safety follow-up visit (up to a maximum of 2 years))

12. Part 1B: Immunogenicity of Bintrafusp alfa Measured by Antidrug Antibody (ADA) Assays (Time Frame - Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen) up to end of safety follow-up visit (up to a maximum of 2 years))

13. Part 1A and 1B: Change from Baseline in QT Interval (Time Frame - From Day 1 Cycle 1 (Baseline) up to Day 1 Cycle 7 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen))

14. Part 1A and IB: Best Overall Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator (Time Frame - From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years))

15. Part 1A and 1B: Duration of Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator (Time Frame - From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years))

16. Part 1A and 1B: Time to Tumor Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator (Time Frame - From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years))

17. Part 1A and 1B: Disease Control According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator (Time Frame - From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years))

18. Part 1A and 1B: Progression-free Survival Time According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator (Time Frame - From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years))

19. Part 1A and 1B: Overall Survival (Time Frame - Time from first treatment to end of study (planned 12 months after last patient started treatment))

Studien-Arme

  • Experimental: Part 1A: M6223 Monotherapy
  • Experimental: Part1B: M6223 + Bintrafusp alfa

Geprüfte Regime

  • M6223:
    Participants will receive an intravenous (IV) infusion of M6223 at escalated doses every 2 weeks (Q2W) on Day 1 of each Cycle (Each cycle is of 14 days) according to the recommendation of the SMC (Safety Monitoring Committee) until the maximum tolerated dose (MTD) has been reached or confirmed disease progression.
  • Bintrafusp alfa:
    Participants will receive an IV infusion of bintrafusp alfa Q2W on Day 1 of each Cycle (Cycle is 14 days) or Q3W on Day 1 of each Cycle (Cycle is of 21 days) until confirmed disease progression.
  • M6223:
    Participants will receive an IV infusion of M6223 at escalated doses Q3W on Day 1 of each Cycle (Each cycle is of 21 days) according to the recommendation of the SMC until the MTD has been reached or confirmed disease progression. Additionally, an every Q3W regimen of M6223 in combination with bintrafusp alfa will be tested after the MTD of M6223 Q2W in combination with bintrafusp alfa has been defined, or after the highest dose level anticipated in the Q2W combination regimen has been tested in at least 3 participants, whichever comes first.

Quelle: ClinicalTrials.gov


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