Clinical trial NCT02118337: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Select Advanced Malignancies
Kidney Cancer
Clear Cell Renal Cell Carcinoma
Keywords: select advanced malignancies,
kidney cancer,
clear cell renal cell carcinoma
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2014-04-21
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This is a multicenter, open-label, Phase 1/2 study to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of MEDI0680 in combination with durvalumab or nivolumab monotherapy in adult immunotherapy-naïve participants with selected advanced malignancies.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase
timeFrame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase
timeFrame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
measure: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase
timeFrame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
measure: Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase
timeFrame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
measure: 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
timeFrame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Secondary outcomes:
measure: Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
measure: Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
measure: Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
measure: Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
measure: Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
measure: Overall Survival in Dose-expansion Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
measure: BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
measure: ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
measure: DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
measure: TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
measure: DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
measure: PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
measure: OS in Dose-escalation Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant)
measure: Number of Participants With TEAEs and TESAEs in Dose-expansion Phase
timeFrame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase
timeFrame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
measure: Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase
timeFrame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
measure: Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase
timeFrame: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
measure: Antitumor Activity of MEDI0680 and Durvalumab Versus Nivolumab Monotherapy in Immunotherapy-Naïve Participants With Advanced or Metastatic Clear-cell Renal Cell Carcinoma (ccRCC) Based on Blinded Independent Central Review (BICR) in Dose-expansion Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
measure: Percent Change From Baseline in Tumor Size in Dose-escalation Phase (Based on Investigator-assessed Modified RECIST v1.1) and Dose-expansion Phase (Based on Investigator-assessed RECIST v1.1)
timeFrame: From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant for dose-escalation phase and approximately 5 years 10 months for dose-expansion phase)
measure: Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases
timeFrame: Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1
measure: Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases
timeFrame: Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1
measure: Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases
timeFrame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)
measure: Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases
timeFrame: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months)
measure: ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase
timeFrame: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Overland Park
country: United States
facility: Research Site
state: Kansas
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: New York
country: United States
facility: Research Site
state: New York
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Hershey
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Seattle
country: United States
facility: Research Site
state: Washington
city: East Bentleigh
country: Australia
facility: Research Site
city: Frankston
country: Australia
facility: Research Site
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Bordeaux
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Paris Cedex 15
country: France
facility: Research Site
city: Villejuif
country: France
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Cardiff
country: United Kingdom
facility: Research Site
city: Southampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: University of Washington
name: Laura Chow, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Angeles Clinic
name: Omid Hamid, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Moffitt Cancer Center
name: Jhanelle Gray, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Providence Cancer Center
name: Rachel Sanborn, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mary Babb Randolph Cancer Center
name: Mohamad Salkeni, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Penn State Hershey Cancer Institute
name: Monika Joshi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: John Theurer Cancer Center
name: Robert Alter, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Peggy Charles Stephenson Cancer Center
name: Raid Aljumaily, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Brown Cancer Center
name: Jason Chesney, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Fernando Quevedo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Memorial Sloan Kettering Cancer Center
name: Martin Voss, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: SCRI Development Innovations, LLC
name: Johanna Bendell
role: PRINCIPAL_INVESTIGATOR
affiliation: Loyola Univ. Medical Center
name: Elizabeth Henry
role: PRINCIPAL_INVESTIGATOR
affiliation: Dartmouth-Hitchcock Medical Center
name: Lionel Lewis
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Brian Rini
role: PRINCIPAL_INVESTIGATOR
affiliation: Menorah Medical Center tour
name: Peter Van Veldhuizen
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.