A Study to Evaluate MEDI0562 in Combination with Immune Therapeutic Agents in Adult Participants with Advanced Solid Tumors

Study identifier:D6060C00002

ClinicalTrials.gov identifier:NCT02705482

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase 1 Multicenter, Open-label, Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, Immunogenicity, and Antitumor Activity of MEDI0562 in Combination with Immune Therapeutic Agents in Adult Subjects with Advanced Solid Tumors

Medical condition

Select advanced solid tumors

Phase

Phase 1

Healthy volunteers

Study drug

MEDI0562, Tremelimumab, Durvalumab

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 100 Years

Date

Study Start Date: 30 Mar 2016

Primary Completion Date: 07 Aug 2019

Study Completion Date: 07 Aug 2019

Study design

Allocation: Non-randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2020 by MedImmune, LLC

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

Participants must meet all of the following criteria:
1. Written and signed informed consent.
2. Age >= 18 years at the time of study entry.
3. Participants must have received and have progressed, are refractory, or are intolerant to standard therapy appropriate for the specific tumor type. Participants should not have received more than 3 prior lines of systemic therapy for recurrent or metastatic.
4. Participants in the dose-escalation phase, must have histologic documentation of advanced solid tumors, excluding primary central nervous system (CNS) tumors and hematologic malignancies.
5. Participants in the dose-expansion phase, must have recurrent or metastatic disease solid tumors according to treatment arm as specified in the protocol.
6. Participants who have received prior therapy with regimens containing cytotoxic T-lymphocyte-associated antigen 4 (CTLA 4), programmed death ligand 1 (PD L1), or programmed death 1 (PD-1) antagonists are permitted to enroll if additional protocol criteria are met.
7. Participants must have at least 1 lesion that is measurable using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines.
8. Participants must consent to provide archived tumor specimens for correlative biomarker studies. In the setting where archival material is unavailable or unsuitable for use, participants must consent and undergo fresh tumor biopsy.
9. All participants are encouraged to consent to and provide both pretreatment and on treatment tumor biopsies.
10. Eastern Cooperative Oncology Group (ECOG) Performance score of 0 or 1, unless protocol exceptions are met.
11. In the opinion of the investigator likely to complete >= 8 weeks of treatment.
12. Adequate hematologic, renal and hepatic function as determined by blood laboratory values.
13. At the time of Day 1 of the study, participants with CNS metastases must have been treated and must be asymptomatic and meet the following:
a. No concurrent treatment, inclusive of, but not limited to surgery, radiation, and/or corticosteroids.
b. At least 42 days without progression of CNS metastases as evidenced by magnetic resonance imaging (MRI) or computed tomography (CT) after last day of treatment.
c. At least 14 days since last dose of corticosteroids.
Note: Participants with leptomeningeal disease or cord compression are excluded from the study.
14. Female participants of childbearing potential who are sexually active with a non-sterilized male partner must use at least 1 highly effective method of contraception from screening, and must agree to continue using such precautions for 180 days after the final dose of study drug.
15. Non-sterilized male participants who are sexually active with a female partner of childbearing potential must use male condom plus, if locally available, spermicide from Day 1 and for 180 days after receipt of the final dose of study drug.

Exclusion Criteria

Any of the following would exclude the participant from participation in the study:
1. Prior treatment with tumor necrosis factor receptor superfamily (TNFRSF) agonists.
2. Prior treatment with immunotherapy (IMT) for certain disease types may be restricted per protocol.
3. History of severe allergic reactions to any unknown allergens or any components of the study drug formulations.
4. Active or prior documented autoimmune disease within the past 2 years.
5. Concurrent enrollment in another clinical study, unless it is an observational clinical study or the follow up period of an interventional study.
6. Receipt of any conventional or investigational anticancer therapy not otherwise specified above within 28 days prior to the first dose.
7. Any concurrent chemotherapy, IMT, or biologic or hormonal therapy for cancer treatment.
8. Unresolved toxicities from prior anticancer therapy.
9. Systemic therapeutic anticoagulation or daily aspirin dose exceeding 325 mg/per day.
10. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of MEDI0562 with exceptions as per protocol.
11. History of primary immunodeficiency, solid organ transplantation, or tuberculosis.
12. Test results indicating active infection with human immunodeficiency virus (HIV) or hepatitis B or C defined by positive serologic testing and confirmatory viral nucleic acid testing.
13. Pregnant or breastfeeding women
14. Major surgery within 4 weeks prior to first dose of MEDI0562 or still recovering from prior surgery.
15. Other invasive malignancy within 2 years with the exception of protocol specified criteria.
16. Any uncontrolled intercurent illness or condition that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of participant safety or study results.

No locations available

Arms	Assigned Interventions
Experimental: MEDI0562 2.25 mg (Q2W) + Durvalumab 1500 mg (Q4W) Participants will receive intravenous (IV) infusion of MEDI0562 2.25 mg every 2 weeks (Q2W) followed by durvalumumab 1500 mg every 4 weeks (Q4W) until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.	Drug: MEDI0562 Participants will receive IV infusion of MEDI0562 2.25 mg or 7.5 mg or 22.5 mg Q2W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation. Drug: Durvalumab Participants will receive IV infusion of durvalumab 1500 mg Q4W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.
Experimental: MEDI0562 7.5 mg (Q2W) + Durvalumab 1500 mg (Q4W) Participants will receive IV infusion of MEDI0562 7.5 mg every 2 weeks (Q2W) followed by durvalumumab 1500 mg every 4 weeks (Q4W) until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.	Drug: MEDI0562 Participants will receive IV infusion of MEDI0562 2.25 mg or 7.5 mg or 22.5 mg Q2W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation. Drug: Durvalumab Participants will receive IV infusion of durvalumab 1500 mg Q4W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.
Experimental: MEDI0562 22.5 mg (Q2W) + Durvalumab 1500 mg (Q4W) Participants will receive IV infusion of MEDI0562 22.5 mg every 2 weeks (Q2W) followed by durvalumumab 1500 mg every 4 weeks (Q4W) until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.	Drug: MEDI0562 Participants will receive IV infusion of MEDI0562 2.25 mg or 7.5 mg or 22.5 mg Q2W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation. Drug: Durvalumab Participants will receive IV infusion of durvalumab 1500 mg Q4W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.
Experimental: MEDI0562 2.25 mg (Q2W) + Tremelimumab 75 mg (Q4W) Participants will receive IV infusion of MEDI0562 2.25 mg Q2W followed by tremelimumab 75 mg Q4W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.	Drug: MEDI0562 Participants will receive IV infusion of MEDI0562 2.25 mg or 7.5 mg or 22.5 mg Q2W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation. Drug: Tremelimumab Participants will receive IV infusion of tremelimumab 75 mg or 225 mg Q4W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.
Experimental: MEDI0562 2.25 mg (Q2W) + Tremelimumab 225 mg (Q4W) Participants will receive IV infusion of MEDI0562 2.25 mg Q2W followed by tremelimumab 225 mg Q4W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.	Drug: MEDI0562 Participants will receive IV infusion of MEDI0562 2.25 mg or 7.5 mg or 22.5 mg Q2W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation. Drug: Tremelimumab Participants will receive IV infusion of tremelimumab 75 mg or 225 mg Q4W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.
Experimental: MEDI0562 7.5 mg (Q2W) + Tremelimumab 225 mg (Q4W) Participants will receive IV infusion of MEDI0562 7.5 mg Q2W followed by tremelimumab 225 mg Q4W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.	Drug: MEDI0562 Participants will receive IV infusion of MEDI0562 2.25 mg or 7.5 mg or 22.5 mg Q2W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation. Drug: Tremelimumab Participants will receive IV infusion of tremelimumab 75 mg or 225 mg Q4W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.
Experimental: MEDI0562 22.5 mg (Q2W) + Tremelimumab 225 mg (Q4W) Participants will receive IV infusion of MEDI0562 22.5 mg Q2W followed by tremelimumab 225 mg Q4W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.	Drug: MEDI0562 Participants will receive IV infusion of MEDI0562 2.25 mg or 7.5 mg or 22.5 mg Q2W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation. Drug: Tremelimumab Participants will receive IV infusion of tremelimumab 75 mg or 225 mg Q4W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.
Experimental: MEDI0562 22.5 mg (Q2W) + Tremelimumab 75 mg (Q4W) Participants will receive IV infusion of MEDI0562 22.5 mg Q2W followed by tremelimumab 75 mg Q4W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.	Drug: MEDI0562 Participants will receive IV infusion of MEDI0562 2.25 mg or 7.5 mg or 22.5 mg Q2W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation. Drug: Tremelimumab Participants will receive IV infusion of tremelimumab 75 mg or 225 mg Q4W until unacceptable toxicity, progressive disease, or development of other reason for treatment discontinuation.

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]