Phase II single-arm study of tepotinib combined with cetuximab (PERSPECTIVE)
- Conditions
- left-sided metastatic colorectal cancer (mCRC)MedDRA version: 21.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-001776-15-BE
- Lead Sponsor
- Merck Healthcare KGaA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 48
Age
1. Are = 18 years of age (or having reached the age of majority according to local laws and regulations, if the age of majority is > 18 years of age) at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2. Advanced (locally advanced or metastatic, unresectable) left sided (from splenic flexure to rectum - National Comprehensive Cancer Network CRC Version 1.2021 guidelines) CRC with RAS/BRAF wild-type at study entry confirmed prior to enrollment, with previous 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.
3. 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).
4. Measurable disease by Investigator in accordance with RECIST Version 1.1.
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
6. Life expectancy > 3 months.
7. 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.
a. For Cohort A in sites outside of US, participants must only have had one prior systemic treatment for mCRC.
b. For Cohort B in sites in the US only, participants must have had at least two prior systemic treatments for mCRC. First-line treatment must include a fluoropyrimidine and oxaliplatin or irinotecan and second-line treatment must include a fluoropyrimidine, oxaliplatin, or irinotecan.
8. Less than 2 months between the last administration of the most recent EGFR containing regimen and first dosing in this study.
9. Adequate hematological function in the absence of transfusions in 7 days before testing defined by white blood cell count = 3 × 109/L with absolute neutrophil count, = 1.5 × 109/L, platelet count = 100 × 109/L, and hemoglobin = 8.5 g/dL.
10. Adequate hepatic function defined by a total bilirubin level = 1.5 × upper limit of normal (ULN), AST = 3 × ULN, and ALT = 3 × ULN. For participants with liver metastases: total bilirubin = 1.5 × ULN, AST/ALT = 5 × ULN.
11. Adequate renal function defined by an estimated glomerular filtration rate > 30 mL/min according to the 4-component Modification of Diet in Renal Disease (MDRD) equation. (GFR [mL/min/1.73 m2] = 175 × serum creatinine (Scr)-1.154 × age 0.203 × 1.212 [if African American] × 0.742 [if female]).
Sex
12. Are male or female
Contraceptive use by males or females will be consistent with local regulations on contraception methods for those participating in clinical studies.
Informed Consent
13. Capable of giving signed informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 44
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4
Medical Conditions
1. 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.
2. Participants who have brain metastasis as the only measurable lesion.
Prior/Concomitant Therapy
3. 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.
Prior/Concurrent Clinical Study Experience
4. 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.
Other Exclusions
5. Known severe hypersensitivity reactions to monoclonal antibodies (Grade = 3 NCI-CTCAE v 5.0), any history of anaphylaxis, or uncontrolled asthma (i.e., 3 or more occurrences of partially controlled asthma).
6. Discontinuation of the most recent cetuximab or panitumumab containing therapy due to an adverse event.
7. Prior treatment with other agents targeting the HGF/MET pathway.
8. Impaired cardiac function:
a. Left ventricular ejection fraction < 45% defined by echocardiography (a screening assessment not required for participants without a history of congestive heart failure unless
clinically indicated)
b. Serious arrhythmia
c. Unstable angina pectoris
d. New York Heart Association heart failure Class III and IV
e. Myocardial infarction within the last 12 months prior to study entry
f. Symptomatic pericardial effusion
g. Corrected QT interval by Fridericia (QTcF) > 480 ms
9. Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 mmHg).
10. Past or current history of neoplasm other than mCRC, except for curatively treated nonmelanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and
with no evidence of disease for at least 5 years.
11. Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the test products.
12. Major surgery within 28 days prior to Day 1 of study intervention.
13. Known infection with human immunodeficiency virus, or an active infection with hepatitis B or hepatitis C virus.
14. Substance abuse, active infection, or other acute or chronic medical or psychiatric condition or laboratory abnormalities that might increase the risk associated with study participation at the discretion of Investigators.
15. IMP use in another study within 3 weeks of the first dose of study intervention.
16. History of ILD or interstitial pneumonitis including radiation pneumonitis that required steroid treatment.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method