Clinical trial NCT05464030: Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors (PROCEADE-CRC-01)
Official title: A Phase I, Multicenter, Open-Label First in Human Study of Anti-CEACAM5 Antibody Drug Conjugate M9140 in Participants With Advanced Solid Tumors (PROCEADE-CRC-01)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Colorectal Cancer
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2022-07-19
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this first-in-human study is to evaluate the safety, tolerability, pharmacokinetics, and preliminary clinical activity of M9140 in advanced solid tumors. This study contains 2 parts: Dose escalation (Part 1) and dose expansion (Part 2).

Study details include:

* Study Duration per participant: Approximately 4 months for Part 1 and 8 months for Part 2
* M9140 is not available through an expanded access program


Eligibility criteria: Inclusion Criteria:

* Participants with documented histopathological diagnosis of locally advanced or metastatic colorectal cancer (CRC), who were intolerant/refractory to or progressed after standard systemic therapies for the advanced/metastatic stage, if locally indicated and available to the participant. Participants with a known microsatellite instability high (MSI-H) status must have received treatment with an immune checkpoint inhibitor (if locally indicated and available) unless contraindicated.
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) below or equal to 1
* Participants with adequate hematologic, hepatic and renal function as defined in protocol
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Participant has a history of malignancy within 3 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertropia, or malignancy that in the opinion of the Investigator, with concurrence with the Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years)
* Participants with known brain metastases, except those meeting the following criteria: Brain metastases that have been treated locally and are clinically stable for at least 4 weeks prior to the start of treatment; No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable)
* Participants with diarrhea (liquid stool) or ileus Grade \> 1
* Participants with active chronic inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease, intestinal perforation) and/or bowel obstruction
* Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] \>= II) or a coronary revascularization procedure within 180 days of study entry. Calculated QTc average (using the Fridericia correction calculation) of \> 470 milliseconds (ms)
* Cerebrovascular accident/stroke (\< 6 months prior to enrollment)
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) and Adverse Events (AEs)
timeFrame: up to 4 months
measure: Part 1: Recommended Dose Expansion (RDE) of M9140
timeFrame: up to 4 months
measure: Parts 2B, 2C and 2D: Number of Participants with Dose Limiting Toxicities (DLTs) and Adverse Events (AEs)
timeFrame: up to 8 months
measure: Part 2A: Number of Participants with Adverse Events (AEs)
timeFrame: up to 8 months
measure: Part 2A: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators
timeFrame: Time from first study treatment throughout the study duration until progressive disease or death up to approximately 8 months
measure: Part 2A: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators
timeFrame: Time from first study treatment to planned assessment at approximately 8 months
Secondary outcomes:
measure: Parts 1, 2A, 2B, 2C and 2D: Pharmacokinetic (PK) Plasma Concentrations of M9140
timeFrame: Part 1: Pre-dose up to 4 months; Part 2: Pre-dose up to 8 months
measure: Parts 1, 2A, 2B, 2C and 2D: Number of Participants with Anti-Drug Antibodies (ADA) Against M9140
timeFrame: Part 1: up to 4 months; Part 2: up to 8 months
measure: Parts 1, 2A, 2B, 2C and 2D: Levels of Titers of Anti-Drug Antibody (ADA) Against M9140
timeFrame: Part 1: up to 4 months; Part 2: up to 8 months
measure: Parts 1 and 2A: Number of Participants with Clinically Significant Changes from Baseline in Triplicate 12-Lead Electrocardiogram (ECG)
timeFrame: Part 1: up to 4 months; Part 2: up to 8 months
measure: Parts 1 and 2A: Change from Baseline in QTc (ΔQTc) Interval
timeFrame: Part 1: baseline, up to 4 months; Part 2: baseline up to 8 months
measure: Parts 1, 2B, 2C: and 2D: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators
timeFrame: Time from first study treatment throughout the study duration until progressive disease or death up to approximately 4 months and 8 months
measure: Parts 1, 2B, 2C and 2D: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator
timeFrame: Time from first study treatment to planned assessment at approximately 4 months and 8 months
measure: Parts 2A, 2B, 2C and 2D: Time to Response
timeFrame: Time from first study treatment to planned assessment at approximately 8 months
measure: Parts 1, 2A, 2B, 2C and 2D: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators
timeFrame: Time from first study treatment to planned assessment at approximately 4 months and 8 months
measure: Part 2A: Overall Survival
timeFrame: Time from first study treatment to planned assessment at approximately 8 months
measure: Part 2A: Number of Participants with Symptomatic Adverse Events (AEs)
timeFrame: up to 8 months
measure: Parts 2A, 2B, 2C and 2D: Number of Participants with Disease Control
timeFrame: At Week 12
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: California Cancer Associates for Research & Excellence, Inc.
state: California
city: Fresno
country: United States
facility: California Cancer Associates for Research & Excellence, Inc.
state: California
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center - Oncology
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
city: Toronto
country: Canada
facility: University Health Network - Princess Margaret Cancer Centre
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital - Dept of Gastroenterology
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
city: Kitaadachi-gun
country: Japan
facility: Saitama Cancer Center
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center Hospital
city: Osakasayama-shi
country: Japan
facility: Kindai University Hospital
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
city: Yokohama-shi
country: Japan
facility: Kanagawa Cancer Center
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
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: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital HM Nou Delfos
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron - VHIR
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: L'Hospitalet de Llobregat
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Centro Integral Oncologico Clara Campal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Quironsalud Madrid - NEXT Oncology
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
Study officials:
affiliation: EMD Serono Research & Development Institute, Inc.
name: Medical Responsible
role: STUDY_DIRECTOR
References: