First-in-Human Study of MS201408-0005A as Single Agent and in Combinations

Study at a glance

From the registry record, last updated by the sponsor on 6 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

Phase I, First-in-Human, Open-Label, Multiple-Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of MS201408-0005A as Single Agent and Sequentially in Combinations With MS201408-0005C or MS201408-0005B in Subjects With Metastatic or Locally Advanced Unresectable Solid Tumors

ClinicalTrials.gov ID

NCT03306420

Acronym / sponsor ID

MS201408-0005

Conditions

Metastatic or Locally Advanced Unresectable Solid Tumors

Keywords

MS201408-0005A, MS201408-0005B, MS201408-0005C, First-in-Human, Advanced solid tumors

Phase

Phase 1

Study type

Interventional

Recruitment status

TerminatedReason stopped: The study was terminated early due to lackluster pharmacodynamic data that showed no significant reduction of plasma kynurenine at steady state of M4112.

Enrolment

15 participants (actual)

Lead sponsor

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

Collaborators

Merck KGaA, Darmstadt, Germany

Study start

3 Oct 2017 (actual)

Primary completion

14 Jan 2019 (actual)

Study completion

14 Jan 2019 (actual)

First posted

11 Oct 2017 (actual)

Results

Posted 6 Feb 2020

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

Non-randomised

Intervention model

Parallel groups

Masking

None (open label)

Number of arms

5

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. Part 1A Dose Escalation: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) as Per National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03

   Time frame: Cycle 1 (Each Cycle is of 28 days)

   DLTs was assessed as per NCI CTCAE v 4.03. DLT defined as any Grade greater than or equal (>=) 3 nonhematological AE or Immune-related adverse event (irAE) assessed by Investigator or Sponsor during first Cycle (first 28 days) of study treatment. Asymptomatic Grade >= 3 lipase or amylase elevation not associated with clinical manifestations of pancreatitis. Any TEAE observed in subsequent cycle. Any Grade 4 neutropenia of >= 5 days duration, Grade >= 3 febrile neutropenia, Grade 3 hemoglobin decrease despite blood transfusion or erythroid growth factor. Grade 4 hemoglobin decrease assessed as related to study drug. Any Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding. Any Grade >= 3 clinical signs and symptoms related to increased QTc.

2. Part 1A Dose Escalation: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Who Experienced a Treatment Related Adverse Events (TRAE) According to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03

   Time frame: Baseline up to safety follow-up visit, assessed up to 15.4 months

   An adverse event (AE) was defined as any untoward medical occurrence in participant which does not necessarily have casual relationship with treatment was any unfavorable and unintended sign(including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. A serious adverse event(SAE) was AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Treatment related AE was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator.

3. Part 1A Dose Escalation: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters

   Time frame: Baseline up to safety follow-up visit, assessed up to 15.4 months

   The laboratory measurements included hematology, biochemistry and hormonal tests. Number of participants with any clinically significant abnormalities in laboratory measurements were reported. Clinical significance was determined by the investigator.

4. Part 1A Dose Escalation: Number of Participants With Clinically Significant Abnormalities in Vital Signs

   Time frame: Baseline up to safety follow-up visit, assessed up to 15.4 months

   Vital signs assessment included blood pressure, pulse rate and body temperature. Number of Participants with any clinically significant abnormalities in vital signs were reported. Clinical significance was determined by the investigator.

5. Part 1A Dose Escalation: Number of Participants With On-Treatment Shift in Eastern Cooperative Oncology Performance Status (ECOG PS) Score From 0 to 1

   Time frame: Baseline up to safety follow-up visit, assessed up to 15.4 months

   ECOG PS score is widely used by doctors and researchers to assess how a participants' disease is progressing, and is used to assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. The score ranges from Grade 0 to Grade 4, where Grade 0 = Fully active, able to carry on all pre-disease performance without restriction, Grade 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (like light house work, office work), Grade 2 = Ambulatory and capable of all self-care but unable to carry out any work activities, Grade 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours and Grade 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. Number of participants with on-treatment shift in ECOG PS Score from 0 to 1 were reported.

6. Part 1A Dose Escalation: Number of Participants With Clinically Significant Change From Baseline in Physical Examination Abnormalities

   Time frame: Baseline up to safety follow-up visit, assessed up to 15.4 months

   A complete physical examination (including, general appearance, skin, pulmonary, cardiovascular, gastrointestinal, external genitourinary only as medically relevant, lymphatic, neurologic and musculoskeletal systems, head/neck, extremities, eyes, ears, nose, throat, and cognitive status) was performed. Number of participants with clinical significant change from baseline in physical examination abnormalities were reported. Clinical significance was determined by the investigator.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2020.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 32843490Naing A, Eder JP, Piha-Paul SA, Gimmi C, Hussey E, Zhang S, Hildebrand V, Hosagrahara V, Habermehl C, Moisan J, Papadopoulos KP. Preclinical investigations and a first-in-human phase I trial of M4112, the first dual inhibitor of indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase 2, in patients with advanced solid tumors. J Immunother Cancer. 2020 Aug;8(2):e000870. doi: 10.1136/jitc-2020-000870.

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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.

3 sites in 1 country: see every site and its status.