Clinical trial NCT02713529: Safety and Efficacy Study of AMG 820 and Pembrolizumab Combination in Select Advanced Solid Tumor Cancer
Official title: A Phase1b/2 Study Assessing Safety and Anti-tumor Activity of AMG 820 in Combination With Pembrolizumab in Select Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pancreatic Cancer
Colorectal Cancer
Non-Small Cell Lung Cancer
Keywords: Solid Tumor
Pancreatic Cancer
Colorectal Cancer
Non-Small Cell Lung Cancer
Lead sponsor: AmMax Bio, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-03-18
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A multi-center Phase 1b/2 study testing the combination of AMG 820 and pembrolizumab in subjects with select advanced solid tumors.

Detailed description: Phase 1b is AMG 820 dose determining and aimed at assessing the safety and tolerability of the selected starting dose of AMG 820 in combination with pembrolizumab. Phase 2 of the study will further evaluate safety and tolerability and additionally test whether AMG 820 can enhance the anti-tumor activity observed historically with pembrolizumab alone and/or overcome lack of response to pembrolizumab monotherapy in subjects with select solid tumors.

Eligibility criteria: Inclusion Criteria:

* Pathologically documented, advanced colorectal, pancreatic or non-small cell lung cancer that is refractory to standard treatment, or the subjects have been intolerant to or refuse standard treatment.
* Measurable disease per RECIST 1.1 guidelines.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
* Adequate hematologic, renal, and hepatic function determined by laboratory blood and urine tests.
* Availability of recent tumor tissue within 3 months prior to enrollment, when feasible.

Exclusion Criteria:

* Has known active central nervous system metastases and/or carcinomatous meningitis.
* History of other malignancy with the past 2 years with some exceptions
* Evidence of active non-infectious pneumonitis/interstitial lung disease
* Evidence of other active autoimmune disease that has required prolonged systemic treatment in past 2 years.
* Evidence of clinically significant immunosuppression such as organ or stem cell transplantation, any severe congenital or acquired cellular and/or humoral immune deficiency, concurrent opportunistic infection.
* Receiving systemic immunostimulatory agents within 6 weeks or 5 half-lives, whichever is shorter, prior to first dose of study treatment (except ant PD-1/PD-L1 treatment if recruited into Group 4a or 4b).
* Evidence of active infection within 2 weeks prior to first dose of study treatment.
* Prior chemotherapy, radiotherapy, biological cancer therapy or major surgery within 28 days prior to enrollment
* Currently participating or has participated in a study (treatment period only) of an investigational agent or used an investigational device within 28 days of enrollment
* Received live vaccine within 28 days prior to enrollment
* Adverse event due to cancer therapy administered more than 28 days prior to enrollment that has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better.
* Positive for human immunodeficiency virus (HIV), Hepatitis B or C
* Women planning to become pregnant or who are lactating/breastfeeding while on study through 4 months after receiving the last dose of study drug.

Primary outcomes:
measure: Participants With Dose Limiting Toxicities (DLT)
timeFrame: The DLT evaluation period was Day 1 to Day 21
measure: Participants With Treatment -Emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2
measure: Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment
timeFrame: Day 1 up to 207 days for Part 1; Day 1 up to 572 days for Part 2
measure: Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment
timeFrame: Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2
measure: Objective Response Rate (ORR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST)
timeFrame: Baseline: Day -28; Treatment: up to Month 13.7
Secondary outcomes:
measure: Time to Response (TTR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) For Participants Who Responded
timeFrame: Day 1 up to Month 16 (max time to censoring)
measure: Time to Progression (TTP) for Participants Who Had Progressive Disease
timeFrame: Day 1 up to 14.4 months (max time to censoring)
measure: Kaplan-Meier Estimates for Overall Survival (OS) at Month 6 and Month 12
timeFrame: Day 1 up to Month 6 or Month 12
measure: Kaplan-Meier Estimates for Progression-Free Survival (PFS) as Per irRECIST at Month 6 and Month 12
timeFrame: Day 1 up to Month 6 or Month 12
measure: AMG 820 Pharmacokinetic Parameter by Dose Group: Time of Maximum Observed Concentration (Tmax) During Treatment Cycles 1 + 2
timeFrame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36
measure: AMG 820 Pharmacokinetic Parameter by Dose Group: Maximum Observed Drug Concentration (Cmax) During Treatment Cycles 1 + 2
timeFrame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36
measure: AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Last (AUClast) During Treatment Cycles 1 + 2
timeFrame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36
measure: AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Over the Dose Interval (AUCtau) During Treatment Cycles 1 + 2
timeFrame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36
measure: AMG 820 Pharmacokinetic Parameter by Dose Group: Minimum Observed Drug Concentration (Cmin) During Treatment Cycles 1 + 2
timeFrame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36
measure: AMG 820 Pharmacokinetic Parameter by Dose Group: Terminal Elimination Half-life (t1/2z) During Treatment Cycles 1 + 2
timeFrame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36
measure: AMG 820 Pharmacokinetic Parameter by Dose Group: Volume of Distribution (Vz) During Treatment Cycles 1 + 2
timeFrame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36
measure: AMG 820 Pharmacokinetic Parameter by Dose Group: Drug Clearance (CL) During Treatment Cycles 1 + 2
timeFrame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36
measure: AMG 820 Pharmacokinetic Parameter by Dose Group: Accumulation Ratio (AR)
timeFrame: Cycle 1, Study Day 1: pre-infusion, at end of infusion, hours 1, 6 and 24 post infusion, Days 5, 8 and 15. Cycle 2, Study Day 22: pre-infusion, at end of infusion, hours 1, 6, 24 post infusion, Days 26, 29 and 36
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Grand Rapids
country: United States
facility: Research Site
state: Michigan
city: New York
country: United States
facility: Research Site
state: New York
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
city: Camperdown
country: Australia
facility: Research Site
state: New South Wales
city: Parkville
country: Australia
facility: Research Site
state: Victoria
city: Wilrijk
country: Belgium
facility: Research Site
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Heidelberg
country: Germany
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Razak AR, Cleary JM, Moreno V, Boyer M, Calvo Aller E, Edenfield W, Tie J, Harvey RD, Rutten A, Shah MA, Olszanski AJ, Jager D, Lakhani N, Ryan DP, Rasmussen E, Juan G, Wong H, Soman N, Smit MD, Nagorsen D, Papadopoulos KP. Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors. J Immunother Cancer. 2020 Oct;8(2):e001006. doi: 10.1136/jitc-2020-001006.