A Phase 1/2, Open-label Study to Evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination with Durvalumab versus Nivolumab Monotherapy in Subjects with Select Advanced Malignancies

Phase 2

Completed

Conditions: clear-cell renal cell carcinoma (ccRCC)
kidney cancer
10038364

Registration Number: NL-OMON47649

Lead Sponsor: MedImmune, LLC, a wholly-owned subsidiary of AstraZeneca PLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 10

Inclusion Criteria

1. Age * 18 years at the time of screening.
2. ECOG performance status of 0 - 1.
3. N/A for NLD as only dose expansion
4. For dose-expansion:
a. Histological confirmation of advanced or metastatic RCC with a clear-cell component
b. Must have received at least 1 and no more than 2 prior anti-angiogenic therapy regimens (including, but not limited to, sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and bevacizumab), in the advanced or metastatic setting.
c.Must have received no more than 3 total prior systemic treatment regimens in the
advanced or metastatic setting, and must have evidence of radiographic progression
on or after the last treatment regimen received and within 6 months prior to study
enrollment.
d. No prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
e. No prior treatment with an mammalian target of rapamycin (mTOR) inhibitor (including, but not limited to everolimus, temsirolimus, sirolimus, and ridaforolimus)
f. Prior cytokine therapy (eg, IL-2, IFN-*) or treatment with cytotoxics is allowed.
g. Subjects must have at least 1 measurable lesion according to RECIST v1.1. A
previously irradiated lesion cannot be considered a target lesion. Radiographic disease assessment can be performed up to 28 days prior to the first dose.;5.Biopsy requirements:
a. N/A for NLD as only dose-expansion
b. Able and willing to give valid written consent for fresh tumor samples if required.
Fresh tumor biopsies should be preferentially obtained from tumor tissues that are safely accessible as determined by the investigator and achieved via non-significant risk procedures (refer to Section 4.3.2.1).
c.. For dose-expansion:
i. Tumor tissue (formalin fixed paraffin embedded [FFPE] archival or fresh tumor tissue) must be received by the central vendor (block or unstained slides) and evaluable for PD-L1 expression status in order to randomize a subject to study treatment.
ii. All subjects are encouraged to consent to and provide both pre-treatment and on- treatment fresh tumor biopsies;however, on-treatment biopsies are optional.;6. For dose-escalation and dose-expansion: (If evaluations performed as part of standard of care for other purposes prior to obtaining informed consent are suitable for screening and occurred within 7 days prior to starting treatment, those evaluations do not need to be repeated if the subject consents to their use):
a. Adequate organ and marrow function, as defined below:
i. Hemoglobin * 9 g/dL
ii. Absolute neutrophil count * 1,500/mm3
iii. Platelet count * 100,000/mm3
iv. Total bilirubin * 1.5 × ULN except subjects with documented Gilbert*s syndrome
(> 3 × ULN) or liver metastasis, who must have a baseline total bilirubin * 3.0 mg/dL
v. Alanine aminotransferase (ALT) and AST * 2.5 × ULN; for subjects with hepatic metastases, ALT and AST * 5 × ULN
vi. Calculated creatine clearance or 24-hour urine creatine clearance * 40mL/min determined by the Cockroft-Gault formula (using actual body weight);7. Written informed consent and any locally required authorization obtained from the subject/legal representative prior to performing any protocol-related procedures, including screening evaluations.;8. Female subjects of childbearing potential who are sexually active with a

Exclusion Criteria

1. Concurrent enrollment in another clinical study, unless in a follow-up period or it is an observational study
2. Central Nervous system (CNS) metastatic disease and leptomeningeal disease are exclused. (NOTE: spinal cord compression which has been stabilized is allowed).
3. Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable
(NOTE: Local treatment of isolated lesions for palliative intent is acceptable [eg, by local surgery or radiotherapy])
4. Any investigational anticancer therapy received within 28 days prior to the first dose of
durvalumab and MEDI0680 or nivolumab.
5. Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of durvalumab and MEDI0680 or nivolumab or still recovering from prior surgery.
6. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v4.03 Grade 0 or 1 with the exception of alopecia and laboratory values listed per the inclusion criteria. Subjects with prior endocrine toxicities (eg, hypothyroidism) who are stable on replacement therapy are not excluded. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by durvalumab and MEDI0680 or nivolumab may be included (eg, hearing loss).
7. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab and MEDI0680 or nivolumab with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
8. Active or prior documented autoimmune or inflammatory disease (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegener*s granulomatosis; Hashimoto syndrome) within the past 3 years. Subjects with vitiligo, alopecia, Grave*s disease, or psoriasis not requiring systemic treatment (within the past 3 years) are not excluded.
9. History of primary immunodeficiency or tuberculosis
10. Test results indicating active infection with human immunodeficiency virus (HIV), or hepatitis A, B, or C
11. Receipt of live, attenuated vaccine within 28 days prior to the first dose of durvlumab and MEDI0680 or nivolumab. NOTE: Subjects, if enrolled, should not receive live vaccine during the study and 90 days after the last dose of durvalumab and MEDI0680 or nivolumab.
12. Females who are pregnant, lactating, or intend to become pregnant during the participation to the study
13. Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, current pneumonitis, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, or psychiatric illness/social situations that would limit compliance with study requirement substantially increase risk of incurring AEs from durvalumab or MEDI0680 or nivolumab, or compromise the ability of the subject to give written informed consent
14. Diagnosis of a second malignancy within the last 2 years prior to Cycle 1, Day 1, with the
exception of those with a negligible risk of metastasis or death, treated with expected
curative outcome (such as adequately treated carcinoma in sit

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary objectives endpoints:<br /><br><br /><br>Dose-expansion:<br /><br>The primary endpoint is objective response (OR) of MEDI0680 in combination with<br /><br>durvalumab versus<br /><br>nivolumab monotherapy. Secondary endpoints include best overall response (BOR),<br /><br>disease control (DC), time<br /><br>to response (TTR), duration of response (DR), progression free survival (PFS),<br /><br>change from baseline in tumor<br /><br>size and overall survival (OS). Efficacy endpoints except OS are based on an<br /><br>application of RECIST v1.1 to<br /><br>investigator-assessed tumor measurements.</p><br>

Secondary Outcome Measures