A Phase I Trial of MK-4280 as Monotherapy and in Combination With Pembrolizumab With or Without Chemotherapy or Lenvatinib (E7080/MK-7902) in Subjects With Advanced Solid Tumors
Study Identifier:
MK-4280-001
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
N/A
Study Contact Information:
Study Complete
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Study Summary
To evaluate safety tolerability and pharmacokinetics study of favezelimab as monotherapy and in combination with pembrolizumab (MK-3475) in adults with metastatic solid tumors for which there is no available therapy which may convey clinical benefit.
To examine the safety, tolerability and efficacy of the favezelimab study drug alone or in combination with pembrolizumab.The study will examine the highest tolerable dose of favezelimab alone or in combination with pembrolizumab, and find out how the body absorbs and breaks favezelimab(also known as pharmacokinetics) alone or when administered in combination with pembrolizumab.
Part A: To evaluate a dose escalation design in which participants receive MK-4280 as monotherapy or MK-4280 in combination with pembrolizumab.
Part B:
To estimate the recommended Phase 2 dose (RP2D), as determined by dose-limiting toxicity, for MK-4280 in combination with pembrolizumab or pembrolizumab and lenvatinib in participants with advanced solid tumors.
To assess the efficacy of MK-4280 as monotherapy; MK-4280 in combination with pembrolizumab with and without chemotherapy; MK-4280 in combination with pembrolizumab and lenvatinib; and MK-4280A as monotherapy in expansion cohorts.
Safety was assessed in all treated pts; efficacy in the full analysis set (FAS) of all treated pts with baseline scan. ORR (RECIST v1.1 by investigator [secondary]), and DOR, PFS, and OS (exploratory).
To evaluate the safety and tolerability of favezelimab alone or in combination with pembrolizumab in patients with MSS MCRC
To evaluate overall response rate (ORR) per RECIST v1.1 by investigator
To evaluate duration of response (DOR), progression-free survival (PFS) per RECIST v1.1 by investigator, and OS
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
18+ years
Study Drug
N/A
Study Status
Indicates the current recruitment status or the expanded access status
Study Complete
Requirements information
Inclusion criteria
- Part A and Part B: Has histologically or cytologically-confirmed metastatic solid tumor Has measurable disease by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) 1.1 criteria. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. Demonstrates adequate organ function If female, is not pregnant or breastfeeding, and if of child-bearing potential, is willing to use an adequate method of contraception for the course of the study and for at least 180 days after the last dose of chemotherapy, 120 days after the last dose of pembrolizumab or favezelimab, or 30 days after the last dose of lenvatinib, whichever occurs last. If male with a female partner(s) of child-bearing potential, both must agree to use an adequate method of contraception starting with the first dose of study drug through 95 days after the last dose of study drug. Note: Abstinence is acceptable if this is the usual lifestyle-preferred contraception for the subject. Voluntarily agree to participate by giving written informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research. Submit an evaluable baseline tumor sample for PD-L1 analysis (either a newly obtained or archival tumor sample) as specified in the Procedure Manual. Part A - Have a histologically or cytologically confirmed metastatic solid tumor for which there is no available therapy that may convey clinical benefit. Non-small cell lung cancer patients (NSCLC) whose disease progressed after platinum-based chemotherapy. Patients with tumors that express mutations in EGFR or ALK will be accepted with a disease that has progressed after FDA-approved treatment. [For the first part of the study, NSCLC patients with a disease that progressed during previous treatment with anti-PD1 / PD-L1] will be accepted]. Part B – Have 1 of the following histologically or cytologically confirmed tumor types: HNSCC that is considered incurable by local therapies. Subjects should have progressed after receiving platinum-containing systemic therapy. Systemic therapy given as part of multimodal treatment for locally advanced disease is allowed. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, larynx, at the bottom of the oropharyngeal or throat, rear wall of the pharynx. Subjects may not have a primary tumor site of nasopharynx (any histology). Subjects enrolled in the PD-1-treatment-naïve HNSCC cohort may not have been treated with prior anti-PD-1/PD-L1 therapy. Subjects enrolled in the PD-1-treatment-failure HNSCC cohort must be refractory to an FDA approved anti-PD-1/PD-L1 monoclonal antibody (mAb) as either monotherapy or in combination with other approved checkpoint inhibitors or other therapies according to their label, defined as (subjects must meet all of the following criteria): Have received at least 2 doses of anti-PD-1/PD-L1 mAb. Have progressive disease after anti-PD-1/PD-L1 mAb defined according to RECIST 1.1. The initial evidence of PD is to be confirmed by a second assessment, no less than 4 weeks from the date of the first documented PD, in the absence of rapid clinical progression. Note: this determination is made by investigator. If PD is confirmed, the initial date of PD documentation will be considered the date of disease progression. Have documented PD within 24 weeks of the last dose of anti-PD-1/PD-L1 mAb. Patients who were re-treated with anti-PD-1/PD-L1 mAb and patients who were on maintenance with anti-PD-1/PD-L1 mAb will be allowed to enter the trial as long as there is documented PD within 24 weeks of the last treatment date (with anti-PD-1/PD-L1 mAb). Adenocarcinoma of the stomach and/or gastric-esophageal junction (GEJ) that is considered inoperable and that has received, and progressed on, at least 1 prior chemotherapy regimen or HER2/neu-targeted approved therapy (if HER2/neu-positive). In both cases, subjects must not have been treated with prior anti-PD-1/PD-L1 therapy. CRC for Arm 1 and Arm 2: CRC originating in either the colon or rectum that is locally advanced unresectable or metastatic (i.e., Stage IV) and that has received, and progressed on, all available standard-of-care therapies including fluoropyrimidine, carbamate, oxaliplatin, and irinotecan but has not been treated with prior anti-PD-1/PD-L1 therapy. CRC for Arm 3 and Arm 4: CRC originating in either the colon or rectum that is locally advanced unresectable or metastatic (i.e., Stage IV) and has been treated with < or = 1 line of systemic therapy but has not been treated with prior anti-PD-1/PD-L1 therapy. Subjects eligible to receive EGFR-targeted therapy must have previously received this treatment in order to be eligible for the study. Note – Subjects with known MSI high or MMR deficient gastric cancer or CRC (as determined by either PCR or IHC) are excluded from participating in this study. MSI high is defined as at least 2 allelic shifts occurring among the 5 analyzed microsatellite markers as detected by PCR. MMR deficient is defined as loss of expression of at least 1 of 4 proteins (MLH1, MSH2, MSH6, and/or PMS2) by IHC. If a subject’s MSI status is unknown, testing is not required to determine eligibility. Note – Subjects who have withdrawn from standard treatment due to unacceptable toxicity warranting discontinuation of that treatment and precluding retreatment with the same agent before progression of disease will also be eligible. Note – Subjects with CRC enrolled into Arm 3 or Arm 4 are not eligible to be re-enrolled in the study on Arm 1 or Arm 2 following discontinuation. Patients with NSCLC metastatic lung cancer after treatment with anti-PD-1 / PD-L1 as well as local-advanced / metastatic kidney cancer (RCC) with clear cells or recurrent cancer.
Exclusion criteria
- Has had chemotherapy, radiation or biological cancer therapy within 4 weeks prior to the first dose of study drug, or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 0 or 1 from the AEs due to cancer therapeutics administered more than 4 weeks earlier (this includes participants with previous immunomodulatory therapy with residual immune-related [ir]AEs).
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.
- Has received previous treatment with another agent targeting the lymphocyte-activation gene 3 (LAG-3) receptor.
- Has received previous treatment with an immunomodulatory therapy (e.g. anti-programmed cell death-1/anti-programmed cell death-ligand 1 [anti-PD-1/anti-PD-L1] or cytotoxic T-lymphocyte-associated protein 4 [CTLA 4] agent) and was discontinued from that therapy due to a Grade 3 or higher irAE.
- Is expected to require any other form of antineoplastic therapy while on study.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy in excess of replacement doses, or on any other form of immunosuppressive medication.
- Has a history of a previous, additional malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years. Time frame exceptions include successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer, or other in situ cancers.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has had a severe hypersensitivity reaction to treatment with another monoclonal antibody.
- Has an active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy.
- Has an active infection requiring therapy.
- Has history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has had a prior stem cell or bone marrow transplant.
- Has a known history of or screens positive for Human Immunodeficiency Virus (HIV), active chronic or acute Hepatitis B or Hepatitis C.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
- Is a regular user as determined by investigator judgement (including "recreational use") of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol), at the time of signing informed consent.
- Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.
- Has clinically significant heart disease that affects normal activities.
- Has received a live-virus vaccine within 30 days of planned start of study drug. Seasonal flu vaccines that do not contain live virus are permitted.
- Subjects being considered for enrollment into Arm 4 with CRC in Part B are also excluded if any of the following additional criteria apply:
- Has plans to use, or is using, any herbal medications/supplements or any medications or foods that are strong inhibitors or inducers of cytochrome P450 3A 4/5 =1 week prior to the start of study treatment.
- Has received previous treatment with irinotecan.
- Has a known diagnosis of Gilbert’s Syndrome.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START San Antonio
San Antonio, TX, United States, 78229
Investigator
Amita Patnaik
Status
Recruitment Complete
Condition(s) Treated at Site
Neoplasms
Location
START Midwest
Grand Rapids, MI, United States, 49546
Investigator
Nehal Lakhani
Status
Recruitment Complete
Condition(s) Treated at Site
Neoplasms