A Study to Evaluate MEDI5752 in Subjects With Advanced Solid Tumors

NCT03530397 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: D7980C000012018-003075-35
• Study Type: interventional
• Target: 401
• Locations: 9 countries
• Sites: 40

Brief Summary

The purpose of this study is to evaluate MEDI5752 and carboplatin and pemetrexed or paclitaxel or nab-paclitaxel in adult subjects with advanced solid tumors, when administered as a single agent or combined with chemotherapy.

Conditions

Selected Advanced Solid Tumors

Keywords

Advanced solid tumors; MEDI5752; immuno-oncology; Cancer; PD-1/CTLA-4 Bispecific; PD-1; CTLA-4; Bispecific; Chemotherapy; Pemetrexed; Carboplatin; Pembrolizumab

Outcome Measures

Primary Outcomes (7)

• The number of subjects experiencing treatment related adverse events (AEs) (Dose-escalation phase)

  The primary endpoint is as assessed by the number of subjects experiencing adverse events (AEs) graded per NCI CTCAE v4.03

  From the time of informed consent through 114 days following termination of treatment with investigational product

• Preliminary anti-tumor activitiy of MEDI5752 (versus pembrolizumab, where applicable) using Objective Response based on RECIST v1.1 (Dose-expansion phase)

  The primary endpoint of antitumor activity include Objective Response and will be based on all post baseline disease assessments that occur prior to initiation of subsequent anticancer therapy.

  From the first dose of study drug through the date of first documented progression, end of study, date of death, or two years after the last patient starts treatment, whichever should occur first

• The number of subjects experiencing dose-limiting toxicities (DLTs) (Dose-escalation phase)

  The primary endpoint is as assessed by the number of subjects experiencing dose limiting toxicities (DLTs) as defined by the protocol.

  Up to 21 days following the first dose

• The number of subjects experiencing abnormal laboratory evaluations (Dose-escalation phase)

  The primary endpoint is as assessed as the number of subjects experiencing changes in laboratory parameters from baseline.

  From the time of informed consent through 114 days following termination of treatment with investigational product

• The number of subjects experiencing changes from baseline in vital signs reported as adverse events (Dose-escalation phase)

  The primary endpoint is as assessed by the number of subjects experiencing clinically significant changes in vital signs from baseline.

  From the time of informed consent through 114 days following termination of treatment with investigational product

• The number of subjects experiencing abnormal electrocardiograms (ECG) reported as Adverse Events (Dose-escalation phase)

  The primary endpoint is as assessed by the the number of subjects experiencing clinically significant changes in ECG parameters from baseline.

  From the time of informed consent through 114 days following termination of treatment with investigational product

• The number of subjects experiencing treatment related serious adverse events (SAEs) (Dose-escalation phase)

  The primary endpoint is as assessed by the number of subjects with serious adverse events (SAEs) graded per NCI CTCAE v4.03.

  From the time of informed consent through 114 days following termination of treatment with investigational product

Secondary Outcomes (15)

• Pharmacokinetics of MEDI5752: Cmax

  To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment

• Pharmacokinetics of MEDI5752: AUC

  To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment

• Pharmacokinetics of MEDI5752: Clearance

  To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment

• Pharmacokinetics of MEDI5752: t 1/2

  To be assessed at Day 1, 2, 3, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment.

• Ability of MEDI5752 to generate immune response in subjects with advanced solid tumors

  To be assessed at Day 1, 8, 15, 22, 29, 43, 64, 85, and 106 over the first 4 months of treatment and up to 114 days following end of treatment.

Study Arms (3)

Arm A: MEDI5752

EXPERIMENTAL

MEDI5752

Biological: MEDI5752

Arm B: MEDI5752 and chemotherapy

EXPERIMENTAL

MEDI5752, pemetrexed, carboplatin and paclitaxel.

Biological: MEDI5752; Drug: Pemetrexed; Drug: Carboplatin; Drug: Paclitaxel or Nab-Paclitaxel

Arm C: Pembrolizumab and chemotherapy

ACTIVE COMPARATOR

pembrolizumab, pemetrexed, and carboplatin

Drug: Pemetrexed; Drug: Carboplatin; Biological: Pembrolizumab

Interventions

MEDI5752 BIOLOGICAL

Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation.

Arm A: MEDI5752; Arm B: MEDI5752 and chemotherapy

Pemetrexed DRUG

Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation

Arm B: MEDI5752 and chemotherapy; Arm C: Pembrolizumab and chemotherapy

Carboplatin DRUG

Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation

Arm B: MEDI5752 and chemotherapy; Arm C: Pembrolizumab and chemotherapy

Pembrolizumab BIOLOGICAL

Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation

Arm C: Pembrolizumab and chemotherapy

Paclitaxel or Nab-Paclitaxel DRUG

Subjects will remain on treatment until unacceptable toxicity, documentation of progressive disease, or development of other reason for treatment discontinuation

Arm B: MEDI5752 and chemotherapy

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at the time of screening
• World Health Organization/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
• Life expectancy ≥ 12 weeks
• Histologically or cytologically-confirmed advanced solid tumors
• Subjects who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy or any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment may be eligible to enter the study following a washout period as applicable
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception
• Nonsterilized males who are sexually active with a female partner of childbearing potential must use a male condom with spermicide where locally available from Day 1 and for 90 days after the final dose of investigational product. Males receiving pemetrexed or carboplatin must use contraception during study treatment and up to 6 months thereafter.
• Subjects must have at least one measurable lesion
• Adequate organ and marrow function
• Written informed consent and any locally required authorization
• Subjects must provide tumor material as applicable

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both MedImmune staff and/or staff at the study site)
• Concurrent enrollment in another clinical study, unless it is an observational clinical study or the follow-up period of an interventional study
• For subjects who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4:
• Subjects must not have received anti-PD-1, anti-PD-L1, anti-CTLA-4 or any other immunotherapy or immune-oncology (IO) agent within 21 days of commencing treatment with investigational product.
• Subject must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
• All AEs while receiving prior immunotherapy must have completely resolved or resolved to Grade 1 prior to screening for this study.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of investigational product is excluded.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of investigational product.
• Active or prior documented autoimmune or inflammatory disorders
• History of active primary immunodeficiency:
• History of organ transplant
• Known allergy or reaction to any component of the planned study treatment.
• Untreated CNS metastatic disease, leptomeningeal disease, or cord compression
• Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of Investigational Product or still recovering from prior surgery
• 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

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (40)

Research Site

Detroit, Michigan, 48202, United States

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Research Site

New York, New York, 10065, United States

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Chapel Hill, North Carolina, 27599, United States

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Providence, Rhode Island, 02903, United States

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Chattanooga, Tennessee, 37404, United States

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Nashville, Tennessee, 37203, United States

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Fairfax, Virginia, 22031, United States

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Melbourne, 3000, Australia

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Melbourne, 3004, Australia

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Randwick, 2031, Australia

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Bordeaux, 33075, France

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Lyon, 69373, France

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Villejuif, 94805, France

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Meldola, 47014, Italy

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Napoli, 80131, Italy

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Ravenna, 48121, Italy

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Roma, 168, Italy

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Amsterdam, 1066 CX, Netherlands

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Lisbon, 1649-035, Portugal

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Porto, 4200-072, Portugal

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Cheongju-si, 28644, South Korea

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Gyeonggi-do, 13620, South Korea

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Incheon, 21565, South Korea

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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A Coruña, 15006, Spain

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Barcelona, 08003, Spain

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Barcelona, 08028, Spain

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Barcelona, 08035, Spain

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Barcelona, 08041, Spain

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Barcelona, 08916, Spain

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Majadahonda, 28222, Spain

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Málaga, 29010, Spain

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Pamplona, 31008, Spain

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Valencia, 46010, Spain

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Taichung, 40705, Taiwan

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Tainan, 70403, Taiwan

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Taipei, 10048, Taiwan

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MeSH Terms

Conditions

Neoplasms; Diabetes Mellitus, Insulin-Dependent, 12

Interventions

Pemetrexed; Carboplatin; pembrolizumab; 130-nm albumin-bound paclitaxel

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals

Study Officials

• Deepa Subramaniam, MD, MSc

  AstraZeneca

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2018
• First Posted: May 21, 2018
• Study Start: April 24, 2018
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: June 24, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

PT (2); AU (3); TW (3); ES (10); NL (1); FR (3); KR (7); IT (4); US (7)