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 Participants With Select Advanced Malignancies

NCT02118337 | Completed Phase 1 Results

• 1 other identifier: D6020C00001
• Study Type: interventional
• Target: 97
• Locations: 6 countries
• Sites: 27

Brief Summary

To evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination with Durvalumab versus Nivolumab Monotherapy in Participants with Select Advanced Malignancies.

Conditions

Select Advanced Malignancies; Kidney Cancer; Clear Cell Renal Cell Carcinoma

Keywords

select advanced malignancies,; kidney cancer,; clear cell renal cell carcinoma

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase

  An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

  Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

• Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase

  Number of participants in dose-escalation phase with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters are defined as any abnormal finding during analysis of serum chemistry, hematology, coagulation, and urine.

  Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

• Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase

  Number of participants in dose-escalation phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight.

  Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

• Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase

  Number of participants in dose-escalation phase with abnormal ECG parameters reported as TEAEs are reported.

  Day 1 through 90 days post end of treatment (approximately 5 years 10 months)

• Objective Response Rate (ORR) Based on Investigator-assessed Response Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Dose-expansion Phase

  The ORR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as \>= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression in-between.

  From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

Secondary Outcomes (24)

• Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

  From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

• Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

  From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

• Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

  From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

• Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

  From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

• Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase

  From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)

Study Arms (9)

MEDI0680 0.1 mg/kg + Durvalumab 3 mg/kg

EXPERIMENTAL

Participants in dose-escalation phase will receive IV infusion of MEDI0680 0.1 mg/kg and durvalumab 3 mg/kg every 2 weeks (Q2W) for up to 12 months.

Biological: MEDI0680; Biological: Durvalumab

MEDI0680 0.1 mg/kg + Durvalumab 10 mg

EXPERIMENTAL

Participants in dose-escalation phase will receive IV infusion of MEDI0680 0.1 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Biological: MEDI0680; Biological: Durvalumab

MEDI0680 0.5 mg/kg + Durvalumab 10 mg

EXPERIMENTAL

Participants in dose-escalation phase will receive IV infusion of MEDI0680 0.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Biological: MEDI0680; Biological: Durvalumab

MEDI0680 2.5 mg/kg + Durvalumab 10 mg

EXPERIMENTAL

Participants in dose-escalation phase will receive IV infusion of MEDI0680 2.5 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Biological: MEDI0680; Biological: Durvalumab

MEDI0680 10 mg/kg + Durvalumab 10 mg

EXPERIMENTAL

Participants in dose-escalation phase will receive IV infusion of MEDI0680 10 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Biological: MEDI0680; Biological: Durvalumab

MEDI0680 20 mg/kg + Durvalumab 10 mg

EXPERIMENTAL

Participants in dose-escalation phase will receive IV infusion of MEDI0680 20 mg/kg and durvalumab 10 mg/kg Q2W for up to 12 months.

Biological: MEDI0680; Biological: Durvalumab

MEDI0680 20 mg/kg

EXPERIMENTAL

Participants in dose-expansion phase will receive IV infusion of MEDI0680 20 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

Biological: MEDI0680

MEDI0680 20 mg/kg + Durvalumab 750 mg

EXPERIMENTAL

Participants in dose-expansion phase will receive IV infusion of MEDI0680 20 mg/kg and durvalumab 750 mg/kg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

Biological: MEDI0680; Biological: Durvalumab

Nivolumab 240 mg

ACTIVE COMPARATOR

Participants in dose-expansion phase will receive IV infusion of nivolumab 240 mg Q2W until unacceptable toxicity, confirmed disease progression, development of other reason for treatment discontinuation, or for a maximum of 2 years, whichever occurred first.

Biological: Nivolumab

Interventions

MEDI0680 BIOLOGICAL

Participants will receive IV infusion of MEDI0680 0.1 or 0.5 or 2.5 or 10 or 20 mg/kg Q2W in dose-escalation phase and 20 mg/kg Q2W in dose-expansion phase.

Also known as: AMP-514

MEDI0680 0.1 mg/kg + Durvalumab 10 mg; MEDI0680 0.1 mg/kg + Durvalumab 3 mg/kg; MEDI0680 0.5 mg/kg + Durvalumab 10 mg; MEDI0680 10 mg/kg + Durvalumab 10 mg; MEDI0680 2.5 mg/kg + Durvalumab 10 mg; MEDI0680 20 mg/kg; MEDI0680 20 mg/kg + Durvalumab 10 mg; MEDI0680 20 mg/kg + Durvalumab 750 mg

Durvalumab BIOLOGICAL

Participants will receive IV infusion of durvalumab 3 and 10 mg Q2W in dose-escalation phase and 750 mg Q2W in dose-expansion phase.

MEDI0680 0.1 mg/kg + Durvalumab 10 mg; MEDI0680 0.1 mg/kg + Durvalumab 3 mg/kg; MEDI0680 0.5 mg/kg + Durvalumab 10 mg; MEDI0680 10 mg/kg + Durvalumab 10 mg; MEDI0680 2.5 mg/kg + Durvalumab 10 mg; MEDI0680 20 mg/kg + Durvalumab 10 mg; MEDI0680 20 mg/kg + Durvalumab 750 mg

Nivolumab BIOLOGICAL

Participants will receive IV infusion of nivolumab 240 mg Q2W in dose-expansion phase.

Nivolumab 240 mg

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be 18 years or older
• Eastern Cooperative Oncology Group performance status of 0-1
• Adequate organ function
• At least 1 prior line of therapy

You may not qualify if:

• Concurrent enrollment in another clinical study, unless in follow-up period or it is an observational study
• Concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
• Prior treatment with immunotherapy

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (27)

Research Site

Los Angeles, California, 90025, United States

Location

Research Site

Tampa, Florida, 33612, United States

Location

Research Site

Overland Park, Kansas, 66209, United States

Location

Research Site

Louisville, Kentucky, 40202, United States

Location

Research Site

Rochester, Minnesota, 55905, United States

Location

Research Site

Hackensack, New Jersey, 07601, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Cleveland, Ohio, 44195, United States

Location

Research Site

Oklahoma City, Oklahoma, 73104, United States

Location

Research Site

Portland, Oregon, 97213, United States

Location

Research Site

Hershey, Pennsylvania, 17033-0850, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Seattle, Washington, 98109, United States

Location

Research Site

East Bentleigh, 3165, Australia

Location

Research Site

Frankston, 3199, Australia

Location

Research Site

Toronto, Ontario, M5G 2M9, Canada

Location

Research Site

Montreal, Quebec, H3T 1E2, Canada

Location

Research Site

Bordeaux, 33075, France

Location

Research Site

Dijon, 21079, France

Location

Research Site

Marseille, 13009, France

Location

Research Site

Paris, 75908, France

Location

Research Site

Villejuif, 94805, France

Location

Research Site

Amsterdam, 1066 CX, Netherlands

Location

Research Site

Groningen, 9713 GZ, Netherlands

Location

Research Site

Cambridge, CB2 0QQ, United Kingdom

Location

Research Site

Cardiff, CF14 2TL, United Kingdom

Location

Research Site

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (1)

• Voss MH, Azad AA, Hansen AR, Gray JE, Welsh SJ, Song X, Kuziora M, Meinecke L, Blando J, Achour I, Wang Y, Walcott FL, Oosting SF. A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Clin Cancer Res. 2022 Jul 15;28(14):3032-3041. doi: 10.1158/1078-0432.CCR-21-4115.

  PMID: 35507017 DERIVED

Related Links

• Redacted Protocol D6020C00001
• Redacted SAP D6020C00001

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

durvalumab; Nivolumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Farzana Walcott
• Organization: MedImmune, LLC

information.center@astrazeneca.com

+1 301-398-3063

Study Officials

• Laura Chow, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

• Omid Hamid, MD

  The Angeles Clinic

  PRINCIPAL INVESTIGATOR

• Jhanelle Gray, MD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

• Rachel Sanborn, MD

  Providence Cancer Center

  PRINCIPAL INVESTIGATOR

• Mohamad Salkeni, MD

  Mary Babb Randolph Cancer Center

  PRINCIPAL INVESTIGATOR

• Monika Joshi, MD

  Penn State Hershey Cancer Institute

  PRINCIPAL INVESTIGATOR

• Robert Alter, MD

  John Theurer Cancer Center

  PRINCIPAL INVESTIGATOR

• Raid Aljumaily, MD

  Peggy Charles Stephenson Cancer Center

  PRINCIPAL INVESTIGATOR

• Jason Chesney, MD

  Brown Cancer Center

  PRINCIPAL INVESTIGATOR

• Fernando Quevedo, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

• Martin Voss, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Johanna Bendell

  SCRI Development Innovations, LLC

  PRINCIPAL INVESTIGATOR

• Elizabeth Henry

  Loyola Univ. Medical Center

  PRINCIPAL INVESTIGATOR

• Lionel Lewis

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

• Brian Rini

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

• Peter Van Veldhuizen

  Menorah Medical Center tour

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: April 11, 2014
• First Posted: April 21, 2014
• Study Start: May 19, 2014
• Primary Completion: March 17, 2020
• Study Completion: March 17, 2020
• Last Updated: June 1, 2021
• Results First Posted: June 1, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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

GB (3); US (13); CA (2); FR (5); NL (2); AU (2)