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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 Feb 2021 → ongoing

Decision date (initial)

2024-06-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2023-509604-15-00

EudraCT number

2019-004338-41

ClinicalTrials.gov

NCT04522323

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Efficacy, Safety, Pharmacodynamic, Others, Pharmacokinetic

Safety:
• Determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of MEDI5752 combined with lenvatinib (Dose-exploration Phase)
• Assess safety and tolerability of MEDI5752 combined with lenvatinib (or axitinib)

Efficacy:
Assess the antitumor activity of MEDI5752 combined with lenvatinib"

Secondary objectives 1

1. "Efficacy: • Assess the antitumor activity of MEDI5752 combined with lenvatinib Pharmacokinetics: • Investigate the pharmacokinetics (PK) of MEDI5752 Immunogenicity: • Investigate the immunogenicity of MEDI5752"

Conditions and MedDRA coding

Advanced Renal Cell Carcinoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. "1. Age ≥ 18 at the time of screening 2. Body weight > 35 kg 3. Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures 4. Histologically or cytologically proven advanced RCC with clear cell component 5. Advanced RCC not previously treated in that setting 6. Provision of tumor material (≥ 5 unstained slides or tissue block) from an archival or fresh tissue biopsy 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 8. Subjects must have at least 1 measurable lesion according to RECIST v1.1 9. Life expectancy ≥ 12 weeks 10. Adequate organ and marrow function (in the absence of transfusions or growth factor support within 14 days prior to enrollment) as defined 11. Female subjects of childbearing potential: (a) Must have negative pregnancy test at screening and prior to each administration of investigational product (b) If sexually active with a nonsterilized male partner, must use at least one highly effective method of birth control from screening to 3 months (ie, 90 days; based on 5 half-lives of MEDI5752 + 6 months) after the last dose of MEDI5752 and 30 days after the last dose of lenvatinib. 12. 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. 13. Nonsterilized male subjects who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to 3 months (90 days) after the last dose of MEDI5752 and 30 days after the last dose of lenvatinib.

Exclusion criteria 1

1. "1. 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 2. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study 3. Previous treatment with mTOR inhibitors, PD-1, PD-L1, or CTLA-4 inhibitors for RCC or any other immune checkpoint inhibitors 4. Previous treatment with VEGF inhibitors 5. Evidence of infections as defined 6. History of organ transplant 7. Active or prior documented autoimmune or inflammatory disorders 8. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of investigational product with listed exceptions to this criterion 9. Poorly controlled blood pressure (BP), defined as 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. 10. Thromboembolic (arterial or venous) events within previous 6 months 11 Any concurrent therapy for cancer including, but not limited to, prohibited medications as listed 12 Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product 13. Untreated or progressive CNS metastatic disease, any leptomeningeal disease, or cord compression 14. History of another primary malignancy exception 15. Major surgery within 4 weeks prior to enrollment or radiation therapy within 2 weeks prior to enrollment, or has not recovered (ie, ≤- Grade 1 or at baseline) from AEs due to prior treatment 16. Female subjects who are pregnant or breastfeeding as well as male or female subjects of reproductive potential who are not willing to employ one highly effective method of birth control as described 17. History of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (NCI CTCAE v5.0 Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted 18. Uncontrolled intercurrent illness within the last 6 months prior to enrollment including, but not limited to, ongoing or active infection, cardiomyopathy of any etiology, symptomatic congestive heart failure (class > 2 as defined by New York Heart Association), uncontrolled hypertension, unstable angina pectoris, history of myocardial infarction, cardiac arrhythmia, interstitial lung disease, serious chronicgastrointestinal conditions associated with diarrhea 19. Uncontrolled intercurrent illness within the last 6 months prior to enrollment including psychiatric illness/social situations that would limit subject's compliance with study requirements, substantially increase subject's risk of incurring AEs or compromise subject's ability to give informed consent 20. Clinically significant gastrointestinal abnormality including: (a) Malabsorption, gastric resection, or any condition that according to investigator might affect absorption of orally taken medication (b) Active gastrointestinal bleeding in past 3 months (c) History of gastrointestinal perforation or gastrointestinal or non-gastrointestinal fistula in past 3 months 21. Serious nonhealing wound, ulcer, or bone fracture 22. 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. 23. Radiographic evidence of major blood vessel invasion/infiltration/encasement"

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. "Safety • Incidence of adverse events (AEs)/serious adverse events (SAEs) • Dose-limiting toxicities (DLTs) • AEs leading to discontinuation of treatment • Abnormal laboratory parameters, vital signs, electrocardiogram (ECG) results Efficacy • Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1"

Secondary endpoints 1

1. "Efficacy • Progression-free survival (PFS), best overall response (BOR), disease control rate (DCR), duration of response (DoR), and time to response (TTR) per RECIST v1.1 Pharmacokinetics • Concentration of MEDI5752 in serum Immunogenicity • Incidence of antidrug antibodies (ADAs) against MEDI5752 in serum "

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Study Information Center

Third parties 8

Locations

2 EU/EEA countries · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications