Safety and Efficacy Study of AMG 820 and Pembrolizumab Combination in Select Advanced Solid Tumor Cancer

A Phase1b/2 Study Assessing Safety and Anti-tumor Activity of AMG 820 in Combination With Pembrolizumab in Select Advanced Solid Tumors

Sponsors

Lead Sponsor: Amgen

Collaborator: Merck Sharp & Dohme Corp.

Source Amgen
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.

Overall Status Completed
Start Date April 14, 2016
Completion Date May 17, 2019
Primary Completion Date January 2, 2019
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Participants With Dose Limiting Toxicities (DLT) The DLT evaluation period was Day 1 to Day 21
Participants With Treatment -Emergent Adverse Events (TEAEs) Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to AMG 820 Treatment Day 1 up to 207 days for Part 1; Day 1 up to 572 days for Part 2
Participants With Treatment -Emergent Adverse Events (TEAEs) Related to Pembrolizumab Treatment Day 1 up to 207 days for Part 1 and Day 1 up to 572 days for Part 2
Objective Response Rate (ORR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) Baseline: Day -28; Treatment: up to Month 13.7
Secondary Outcome
Measure Time Frame
Time to Response (TTR) Per Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) For Participants Who Responded Day 1 up to Month 16 (max time to censoring)
Time to Progression (TTP) for Participants Who Had Progressive Disease Day 1 up to 14.4 months (max time to censoring)
Kaplan-Meier Estimates for Overall Survival (OS) at Month 6 and Month 12 Day 1 up to Month 6 or Month 12
Kaplan-Meier Estimates for Progression-Free Survival (PFS) as Per irRECIST at Month 6 and Month 12 Day 1 up to Month 6 or Month 12
AMG 820 Pharmacokinetic Parameter by Dose Group: Time of Maximum Observed Concentration (Tmax) During Treatment Cycles 1 + 2 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
AMG 820 Pharmacokinetic Parameter by Dose Group: Maximum Observed Drug Concentration (Cmax) During Treatment Cycles 1 + 2 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
AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Last (AUClast) During Treatment Cycles 1 + 2 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
AMG 820 Pharmacokinetic Parameter by Dose Group: Area Under the Curve Over the Dose Interval (AUCtau) During Treatment Cycles 1 + 2 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
AMG 820 Pharmacokinetic Parameter by Dose Group: Minimum Observed Drug Concentration (Cmin) During Treatment Cycles 1 + 2 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
AMG 820 Pharmacokinetic Parameter by Dose Group: Terminal Elimination Half-life (t1/2z) During Treatment Cycles 1 + 2 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
AMG 820 Pharmacokinetic Parameter by Dose Group: Volume of Distribution (Vz) During Treatment Cycles 1 + 2 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
AMG 820 Pharmacokinetic Parameter by Dose Group: Drug Clearance (CL) During Treatment Cycles 1 + 2 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
AMG 820 Pharmacokinetic Parameter by Dose Group: Accumulation Ratio (AR) 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
Enrollment 117
Condition
Intervention

Intervention Type: Biological

Intervention Name: AMG820 and pembrolizumab

Description: Treatment with AMG820 and pembrolizumab

Arm Group Label: AMG820 and pembrolizumab

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
MD Study Director Amgen
Location
Facility:
Research Site | Atlanta, Georgia, 30332, United States
Research Site | Boston, Massachusetts, 02114, United States
Research Site | Boston, Massachusetts, 02215, United States
Research Site | Grand Rapids, Michigan, 49546, United States
Research Site | New York, New York, 10021, United States
Research Site | Philadelphia, Pennsylvania, 19111, United States
Research Site | Greenville, South Carolina, 29605, United States
South Texas Accelerated Research Therapeutics | San Antonio, Texas, 78229, United States
Research Site | Camperdown, New South Wales, 2050, Australia
Research Site | Parkville, Victoria, 3050, Australia
Research Site | Wilrijk, 2610, Belgium
Princess Margaret Cancer Centre | Toronto, Ontario, M5G 2M9, Canada
Research Site | Heidelberg, 69120, Germany
Research Site | Madrid, 28040, Spain
Research Site | Madrid, 28050, Spain
Location Countries

Australia

Belgium

Canada

Germany

Spain

United States

Verification Date

July 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: AMG820 and pembrolizumab

Type: Experimental

Description: Treatment with AMG820 and pembrolizumab

Patient Data Yes
Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov