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Study of Tepotinib Combined With Cetuximab in Participants With Left-Sided RAS/BRAF Wild Type Metastatic Colorectal (PERSPECTIVE)

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ClinicalTrials.gov Identifier: NCT04515394
Recruitment Status : Recruiting
First Posted : August 17, 2020
Last Update Posted : May 7, 2021
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Brief Summary:
The purpose of this study is to assess the preliminary antitumor activity, safety and tolerability of tepotinib in combination with cetuximab in participants with RAS/BRAF wild-type left-sided Metastatic Colorectal Cancer (mCRC) having acquired resistance to anti-epidermal growth factor receptor (EGFR) antibody targeted therapy due to mesenchymal epithelial transition (MET) amplification.

Condition or disease Intervention/treatment Phase
Colorectal Neoplasms Drug: Tepotinib Biological: Cetuximab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Single-Arm Study to Investigate Tepotinib Combined With Cetuximab in RAS/BRAF Wild-Type Left-Sided mCRC Patients Having Acquired Resistance to Anti-EGFR Antibody Targeting Therapy Due to MET Amplification (PERSPECTIVE)
Actual Study Start Date : January 28, 2021
Estimated Primary Completion Date : March 23, 2023
Estimated Study Completion Date : March 23, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Cetuximab

Arm Intervention/treatment
Experimental: Tepotinib + Cetuximab Drug: Tepotinib
Participants will receive Tepotinib initially at 500 milligrams (mg) once daily (QD) (2 film coated tablets of 250 mg QD). For potential dose de-escalation, the available 250 mg dose strength will be used (1 tablet once daily) until disease progression (according to Response Evaluation Criteria in Solid Tumors Version 1.1 [RECIST v1.1]), death, Adverse event (AE) leading to discontinuation, study withdrawal, or withdrawal of consent, whichever occurs first.
Other Name: MSC2156119J

Biological: Cetuximab
Cetuximab, is administered at an initial dose of 400 milligrams per square meter (mg/m^2) body surface area, over a recommended intravenous infusion period of 120 minutes and a maximum infusion rate of 5 milligrams per minute (5 mg/min), followed by or starting with weekly infusions at a dose of 250 mg/m^2 over a recommended infusion period of 60 minutes and a maximum infusion rate of 10 mg/min until disease progression, death, Adverse event (AE) leading to discontinuation of both study interventions, study withdrawal, or withdrawal of consent, whichever occurs first.
Other Names:
  • Erbitux®
  • MSB0010442D




Primary Outcome Measures :
  1. Number of Participants Experiencing Dose Limiting Toxicities (DLTs) According to National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) for Adverse Events (AEs) Version 5.0 [ Time Frame: Day 1 to Day 21 of Cycle 1 (each cycle is of 21 days) ]
  2. Number of Participants with Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1) Assessed by Investigators [ Time Frame: Time from first study treatment assessed up to 556 days ]

Secondary Outcome Measures :
  1. Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1) Assessed by Investigators [ Time Frame: Time from first study treatment assessed up to 556 days ]
  2. Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1) Assessed by Investigators [ Time Frame: Time from first study treatment assessed up to 556 days ]
  3. Overall Survival (OS) Assessed by Investigators [ Time Frame: Time from first study treatment assessed up to 556 days ]
  4. Number of Participants with Adverse Events (AEs) and Treatment Related Adverse Events (TRAEs) [ Time Frame: Time from first study treatment up to 30 days after the last dose, assessed up to 221 days ]
  5. Number of Participants With Clinically Significant Changes in Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings [ Time Frame: Time from first study treatment up to 30 days after the last dose, assessed up to 221 days ]
    Number of participants with clinically significant changes in vital signs, laboratory parameters and 12-lead ECG will be reported.

  6. Number of Participants With Anti-Drug Antibodies (ADAs) for Cetuximab [ Time Frame: At Day 1 of cycle 1 (each cycle is of 21 days) and at End of Treatment (14 days after last dose, assessed up to 205 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Advanced (locally advanced or metastatic) left sided (from splenic flexure to rectum - National Comprehensive Cancer Network [NCCN] version 4.2020) colorectal cancer (CRC) with RAS/BRAF wild-type at study entry confirmed prior to enrollment, with previous anti-epidermal growth factor receptor (anti-EGFR) therapy and acquired resistance on the most recent anti-EGFR monoclonal antibody therapy (panitumumab or cetuximab) by radiological documentation of disease progression according to RECIST Version 1.1
  • Mesenchymal epithelial transition (MET) amplification detected by a positive liquid biopsy and/or tissue with appropriate regulatory status (collected after disease progression of the previous anti-EGFR therapy)
  • Measurable disease by Investigator in accordance with RECIST Version 1.1
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
  • Life expectancy greater than 3 months
  • Participants having at least one systemic treatment for mCRC including 1 anti-EGFR monoclonal antibody therapy as the most recent line of therapy for mCRC before study treatment and must have shown a radiologically confirmed by RECIST Version 1.1 complete response (CR) or partial response (PR), both for at least 4 months or stable disease (SD) for at least 6 months to that therapy prior to disease progression
  • Less than 2 months between the last administration of the most recent EGFR containing regimen and first dosing in this study
  • Adequate hematological function, hepatic and renal functions as defined in the protocol
  • Signed and dated informed consent indicating that the participants had been informed of all the pertinent aspects of the trial prior to enrollment
  • Contraceptive use by males or females will be consistent with local regulations on contraception methods for those participating in clinical studies
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Participants with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS metastases. Also excluded are participants with carcinomatous meningitis
  • Participants who have brain metastasis as the only measurable lesion
  • Prior chemotherapy, biological therapy, radiation therapy, hormonal therapy for anti-cancer purposes, targeted therapy, or other investigational anticancer therapy (not including palliative radiotherapy at focal sites) within 21 days prior to the first dose of study intervention, except for the anti-EGFR containing regimen including associated chemotherapy if applicable, which may be continued until enrollment of the participant in the study
  • Any unresolved toxicity Grade 2 or more according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, from previous anticancer therapy excluding neuropathy, alopecia and rash
  • Severe hypersensitivity reactions to monoclonal antibodies (Grade greater than or equal to [>=] 3 NCI-CTCAE v 5.0), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more occurrences of partially controlled asthma)
  • Discontinuation of the most recent cetuximab or panitumumab containing therapy due to an adverse event
  • Prior treatment with other agents targeting the hepatocyte growth factor (HGF)/Mesenchymal epithelial transition (MET) pathway
  • Impaired cardiac function: Left ventricular ejection fraction less than [<] 45 percent [%] defined by echocardiography (a screening assessment not required for participants without a history of congestive heart failure unless clinically indicated); Serious arrhythmia; Unstable angina pectoris; New York Heart Association heart failure Class III and IV; Myocardial infarction within the last 12 months prior to study entry and Symptomatic pericardial effusion; Corrected QT interval by Fridericia (QTcF) greater than (>) 480 milliseconds (ms)
  • Hypertension uncontrolled by standard therapies (not stabilized to less than [< ]150/90 millimeter of mercury [mmHg])
  • History of neoplasm other than mCRC
  • History of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the test products
  • Known infection with human immunodeficiency virus, or an active infection with hepatitis B or hepatitis C virus
  • Major surgery within 28 days prior to Day 1 of study intervention
  • History of Interstitial lung disease (ILD) or interstitial pneumonitis including radiation pneumonitis that required steroid treatment
  • Other protocol defined exclusion criteria could apply

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04515394


Contacts
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Contact: US Medical Information 888-275-7376 eMediUSA@emdserono.com
Contact: Communication Center +49 6151 72 5200 service@emdgroup.com

Locations
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Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Additional Information:
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Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT04515394    
Other Study ID Numbers: MS202202_0002
2020-001776-15 ( EudraCT Number )
First Posted: August 17, 2020    Key Record Dates
Last Update Posted: May 7, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.emdgroup.com/en/research/our-approach-to-research-and- development/healthcare/clinical-trials/commitment-responsible-data-sharing.html

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
Colorectal cancer
RAS wild-type
Tepotinib
Cetuximab
Erbitux
Epidermal growth factor receptor resistance
Hepatocyte growth factor
Panitumumab
Mesenchymal epithelial transition
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Antineoplastic Agents, Immunological
Antineoplastic Agents