Clinical trial NCT04522323: A Study to Evaluate MEDI5752 and Axitinib in Subjects With Advanced Renal Cell Carcinoma
Official title: A Phase 1b, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI5752 in Combination With Axitinib in Subjects With Advanced Renal Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Renal Cell Carcinoma
Keywords: renal cell carcinoma
MEDI5752
PD-1/CTLA-4 bispecific
PD-1
CTLA-4
bispecific
axitinib
lenvatinib
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2020-08-21
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 101
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate MEDI5752 in combination with Lenvatinib (or Axitinib), in subjects with advanced renal cell carcinoma.

Detailed description: The purpose of this Phase 1b study is to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity of MEDI5752 in combination with Lenvatinib (or Axitinib) in subjects with advanced renal cell carcinoma.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 at the time of screening
* Body weight \> 35 kg
* Written informed consent
* Histologically or cytologically proven advanced RCC with clear cell component
* Advanced RCC not previously treated in that setting
* Provision of tumor material (≥ 5 unstained slides or tissue block) from an archival or fresh tissue sample
* ECOG performance status of 0 or 1
* Subjects must have at least 1 measurable lesion according to RECIST v1.1
* Life expectancy ≥ 12 weeks
* Adequate organ and marrow function
* Female subjects of childbearing potential must have negative pregnancy test at screening and prior to each administration of investigational product, and must use at least one highly effective method of contraception.
* Strongly recommend nonsterilized male partners of female subjects of childbearing potential use a male condom plus spermicide from screening to 7.6 months after the last dose of MEDI5752 and 30 days after the last dose of lenvatinib.

Exclusion Criteria:

* Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results
* Concurrent enrollment in another clinical study, unless it is an observational study.
* Previous treatment with mTOR inhibitors, PD-1, PD-L1, or CTLA-4 inhibitors for RCC or any other immune checkpoint inhibitor
* Previous treatment with VEGF inhibitors
* Evidence of the following infections: active infection including tuberculosis, human immunodeficiency virus, chronic or active hepatitis B or chronic or active hepatitis C
* History of organ transplant
* Active or prior documented autoimmune or inflammatory disorders
* Current or prior use of immunosuppressive medication within 14 days prior to the first dose of investigational product.
* Poorly controlled blood pressure (BP) defined as systolic BP ≥ 140/90 mmHg at screening and not able to be controlled prior to Cycle 1 Day 1 and any change in antihypertensive medications within 1 week prior to Cycle 1 Day 1.
* Thromboembolic (arterial or venous) events within previous 6 months
* Any concurrent therapy for cancer
* Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product
* Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s)
* Untreated or progressive CNS metastatic disease, any leptomeningeal disease, or cord compression
* History of another primary malignancy
* Unresolved toxicities from previous anticancer therapy
* Major surgery within 4 weeks prior to enrollment or radiation therapy within 2 weeks prior to enrollment or has not recovered from AEs due to prior treatment
* Female subjects must not breastfeed and must not donate, or retrieve for their own use, ova from screening to 3 months after the last dose of MEDI5752 and 30 days after the last dose of lenvatinib.
* History of arrhythmia which is symptomatic or requires treatment, symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
* Uncontrolled intercurrent illness within the last 6 months prior to enrollment
* Clinically significant gastrointestinal abnormality
* Serious nonhealing wound, ulcer, or bone fracture
* Has clinically significant hemoptysis (at least 0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks before the first dose of investigational product
* Radiographic evidence of major blood vessel invasion/infiltration/encasement

Primary outcomes:
measure: Number of subjects experiencing adverse events (AEs)/serious adverse events (SAEs)
timeFrame: Informed consent through 90-Day Post Last Dose.
measure: Number of Participants With Dose Limiting Toxicities (DLT) of MEDI5752 and Lenvatinib (or Axitinib) during the Dose Exploration period.
timeFrame: Informed consent through the first 21 days of treatment with MEDI5752 and Lenvatinib (or Axitinib) in the Dose Exploration Period.
measure: Number of subjects experiencing adverse events (AEs) leading to discontinuation.
timeFrame: Informed consent through 90-Day Post Last Dose.
measure: Number of subjects experiencing abnormal laboratory evaluations.
timeFrame: Informed Consent through 90 post treatment date.
measure: Number of subjects experiencing changes in vital signs reported as Adverse Events.
timeFrame: Informed consent through 90-Day Post Last Dose
measure: Number of subjects experiencing abnormal electrocardiograms (ECG) reported as Adverse Events.
timeFrame: Informed consent through 90-Day Post Last Dose
measure: Preliminary antitumor activity of MEDI5752 combined with Lenvatinib (or Axitinib) by Objective response rate per RECIST version (v) 1.1.
timeFrame: First subject enrolled through 18 months from last subject enrolled, an average of 30 months.
Secondary outcomes:
measure: Antitumor activity of MEDI5752 combined with Lenvatinib by measuring the progression free survival (PFS) according to RECIST v1.1.
timeFrame: Last Subject Enrolled through study completion, an average of 48 months.
measure: Antitumor activity of MEDI5752 combined with Lenvatinib by measuring the Best Overall Response (BOR) according to RECIST v1.1.
timeFrame: First subject enrolled through 18 months from last subject enrolled, an average of 30 months.
measure: Antitumor activity of MEDI5752 combined with Lenvatinib by measuring the Disease Control Rate (DCR).
timeFrame: Informed Consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
measure: Antitumor activity of MEDI5752 combined with Lenvatinib by measuring the Duration of Response (DOR) according to RECIST v1.1.
timeFrame: Informed Consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
measure: Antitumor activity of MEDI5752 combined with Lenvatinib by measuring the Time to Response (TTR) according to RECIST v1.1.
timeFrame: Informed Consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
measure: Pharmacokinetics of MEDI5752: Cmax
timeFrame: Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle
measure: Pharmacokinetics of MEDI5752: AUC
timeFrame: Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle
measure: Pharmacokinetics of MEDI5752: Cmin
timeFrame: Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle
measure: Pharmacokinetics of MEDI5752: t 1/2
timeFrame: Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle
measure: Pharmacokinetics of MEDI5752: Clearance
timeFrame: Day 1, 8, 15, 22, 64 and then Day 1 of every other cycle
measure: Immunogencity of MEDI572: Incidence of ADAs against MEDI5752
timeFrame: Day 1, 8, 15, 22, 30, 64 and then Day 1 of every other cycle
Other outcomes:
Locations:
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: New York
country: United States
facility: Research Site
state: New York
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Hershey
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Frankston
country: Australia
facility: Research Site
city: Waratah
country: Australia
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Córdoba
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Sabadell
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Valencia
country: Spain
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: AstraZeneca Early Oncology
role: STUDY_DIRECTOR
References: