A Study to Evaluate MEDI0562 in Combination With Immune Therapeutic Agents in Adult Subjects With Advanced Solid Tumors

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02705482
• Date of registration: 22/09/2015
• Prospective Registration: Yes
• Primary sponsor: MedImmune LLC
• Public title: A Study to Evaluate MEDI0562 in Combination With Immune Therapeutic Agents in Adult Subjects With Advanced Solid Tumors
• Scientific 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
• Date of first enrolment: March 30, 2016
• Target sample size: 58
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02705482
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Australia, France, Netherlands, Spain, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

Subjects must meet all of the following criteria:

1. Written and signed informed consent.

2. Age = 18 years at the time of study entry.

3. Subjects must have received and have progressed, are refractory, or are intolerant to
standard therapy appropriate for the specific tumor type. Subjects should not have
received more than 3 prior lines of systemic therapy for recurrent or metastatic.

4. Subjects in the dose-escalation phase, must have histologic documentation of advanced
solid tumors, excluding primary CNS tumors and hematologic malignancies.

5. Subjects in the dose-expansion phase, must have recurrent or metastatic disease solid
tumors according to treatment arm as specified in the protocol.

6. Subjects who have received prior therapy with regimens containing CTLA 4, PD L1, or PD
1 antagonists are permitted to enroll if additional protocol criteria are met.

7. Subjects must have at least 1 lesion that is measurable using RECIST guidelines.

8. Subjects must consent to provide archived tumor specimens for correlative biomarker
studies. In the setting where archival material is unavailable or unsuitable for use,
subjects must consent and undergo fresh tumor biopsy.

9. All subjects are encouraged to consent to and provide both pretreatment and on
treatment tumor biopsies.

10. 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, subjects with CNS metastases must have been treated
and must be asymptomatic and meet the following:

1. No concurrent treatment, inclusive of, but not limited to surgery, radiation,
and/or corticosteroids

2. 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

3. At least 14 days since last dose of corticosteroids Note: Subjects with
leptomeningeal disease or cord compression are excluded from the study.

14. Female subjects 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 investigational product.

15. Non-sterilized male subjects 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 investigational
product.

Exclusion Criteria:

Any of the following would exclude the subject from participation in the study:

1. Prior treatment with TNFRSF agonists

2. Prior treatment with 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 investigational product or
interpretation of subject safety or study results.



Age minimum: 18 Years
Age maximum: 100 Years
Gender: All

Health Condition(s) or Problem(s) studied

Select Advanced Solid Tumors

Intervention(s)

Biological: Durvalumab

Biological: Tremelimumab

Biological: MEDI0562

Primary Outcome(s)

Safety as defined by the presence of adverse events (AE), serious adverse events (SAE), and dose limiting toxicities (DLT). [Time Frame: From time of informed consent through 12 weeks after ending treatment with investigational product]

Secondary Outcome(s)

Immunogenicity [Time Frame: At approximately 8 time points through Day 113.]

Preliminary Antitumor Activity: Duration of Response [Time Frame: At approximately 3 time points through Day 113.]

Pharmacokinetics of MEDI0562/durvalumab or MEDI0562/tremelimumab: AUC [Time Frame: To be assessed at approximately 12 clinic visits through Day 113]

Pharmacokinetics of MEDI0562/durvalumab or MEDI0562/tremelimumab: t½ [Time Frame: To be assessed at approximately 12 clinic visits through Day 113]

Preliminary Antitumor Activity: Time to Response [Time Frame: At approximately 3 time points through Day 113.]

Pharmacodynamic Activity [Time Frame: At approximately 12 time points through Day 113.]

Pharmacokinetics of MEDI0562/durvalumab or MEDI0562/tremelimumab: Clearance [Time Frame: To be assessed at approximately 12 clinic visits through Day 113]

Preliminary Antitumor Activity: Overall Survival [Time Frame: At approximately 3 time points through Day 113.]

Preliminary Antitumor Activity: Progression-free Survival [Time Frame: At approximately 3 time points through Day 113.]

Preliminary Antitumor Activity: Objective Response [Time Frame: At approximately 3 time points through Day 113.]

Pharmacokinetics of MEDI0562/durvalumab or MEDI0562/tremelimumab: Cmax [Time Frame: To be assessed at approximately 12 clinic visits through Day 113]

Preliminary Antitumor Activity: Percent Change from Baseline [Time Frame: At approximately 3 time points through Day 113.]

Preliminary Antitumor Activity: Disease Control [Time Frame: At approximately 3 time points through Day 113.]

Preliminary Antitumor Activity:Best Overall Response [Time Frame: At approximately 3 time points through Day 113.]

Secondary ID(s)

D6060C00002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors