A Study of ABBV-927 and ABBV-181, an Immunotherapy, in Participants With Advanced Solid Tumors

Advanced Solid Tumors Cancer Clinical Trial

Official title:

A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-927 and ABBV-181, an Immunotherapy, in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02988960
• Other study ID #: M15-862
• Secondary ID: 2016-002219-16
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: February 22, 2017
• Est. completion date: March 29, 2024

Study information

• Verified date: January 2024
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a dose-escalation study designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of ABBV-927, and to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 in participants with advanced solid tumors.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 163
• Est. completion date: March 29, 2024
• Est. primary completion date: March 29, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
• Participants have adequate bone marrow, kidney and liver function.
• Participants with a history of chronic heart failure or significant cardiovascular disease must have an echocardiogram or multigated acquisition scan indicating left ventricular ejection fraction greater than or equal to 45% within 28 days prior to the first dose of study drug.
• Participants must have creatinine clearance greater than or equal to 50 mL/min as measured by 24-hour urine or estimated by the Cockcroft-Gault formula.
• Participants must have total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN), and aspartate aminotransferase and alanine aminotransferase less than or equal to 2.5 times ULN.
• Participants in all monotherapy arms must have an advanced solid tumor that has progressed on standard therapies known to provide clinical benefit or the participants are intolerant to such therapies.
• Participants in all combination therapy arms must have recurrent or metastatic HNSCC or NSCLC and previously received platinum-based therapy and progressed either during or after anti-programmed death ligand 1 (PDL1)-based therapy. In addition, participants must have received only one prior immunotherapy.
• The Sponsor may decide to limit the specific tumor types selected or treatment settings for specific arms based on evidence gathered.

Exclusion Criteria:

• Participant must not have an active or prior documented autoimmune disease in the last 2 years.
• Participant must not have current or prior use of immunosuppressive medication within 14 days prior to the first dose (with certain exceptions).
• Participant must not have a history of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic leukemia, solid organ transplantation, previous clinical diagnosis of tuberculosis, inflammatory bowel disease, interstitial lung disease, or immune-mediated pneumonitis.
• Participant must not have a history of clinically significant uncontrolled condition(s) including but not limited to the following: uncontrolled hypertension; symptomatic congestive heart failure; unstable angina pectoris or cardiac arrhythmia including atrial fibrillation.
• Participant must not have a history of coagulopathy or a platelet disorder associated with significant clinical risk of thromboembolic event in the judgement of the investigator, or major thromboembolic event within 6 months prior to the first dose of study treatment.
• Participant must not have a prior grade greater than or equal to 3 immune-mediated neurotoxicity or pneumonitis while receiving immunotherapy.
• Participant must not have a known uncontrolled malignancy of the central nervous system.
• Participants in all combination therapy arms must not have a history of exposure to an immunotherapy experiencing an immune-mediated adverse event that required permanent discontinuation of the immunotherapy.
• Female participants must not be pregnant, breastfeeding or considering becoming pregnant during the study or for at least 3 or 5 months (for monotherapy and combination therapy participants, respectively) after the last dose of study drug.
• Male participants must not be considering fathering a child or donating sperm during the study or for at least 3 or 5 months (for monotherapy and combination therapy participants, respectively) after the last dose of study drug.
• Participant is judged by the investigator to have evidence of hemolysis.
• For Japan only, participants with a history of interstitial lung disease (pneumonitis) or current interstitial lung disease (pneumonitis).

Related Conditions & MeSH terms

• Advanced Solid Tumors Cancer
• Neoplasms

Intervention

Drug:
• ABBV-927
Intravenous
• ABBV-927
Intratumoral
• ABBV-181
Intravenous

Locations

Country	Name	City	State
Australia	Peninsula Oncology Centre /ID# 164372	Frankston	Victoria
Australia	Austin Health /ID# 171189	Heidelberg	Victoria
Canada	Princess Margaret Cancer Centre /ID# 200819	Toronto	Ontario
France	Institut Bergonie /ID# 162665	Bordeaux	Gironde
France	Centre Leon Berard /ID# 162663	Lyon CEDEX 08	Rhone
France	Duplicate_Institut Regional du Cancer /ID# 163609	Montpellier CEDEX 5	Herault
France	Institut Gustave Roussy /ID# 162666	Villejuif Cedex	Val-de-Marne
Japan	National Cancer Center Hospital /ID# 217758	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East /ID# 216870	Kashiwa-shi	Chiba
Korea, Republic of	Seoul National University Hospital /ID# 166291	Seoul
Korea, Republic of	Yonsei University Health System Severance Hospital /ID# 166292	Seoul	Seoul Teugbyeolsi
Spain	Hospital Universitario Fundacion Jimenez Diaz /ID# 200128	Madrid
Spain	Hospital Universitario HM Sanchinarro /ID# 200127	Madrid
Spain	Hospital Universitario Puerta de Hierro, Majadahonda /ID# 200129	Majadahonda	Madrid
Spain	Hospital Universitario y Politecnico La Fe /ID# 200975	Valencia
United States	Massachusetts General Hospital /ID# 155267	Boston	Massachusetts
United States	The University of Chicago Medical Center /ID# 155264	Chicago	Illinois
United States	Virginia Cancer Specialists - Fairfax /ID# 155266	Fairfax	Virginia
United States	University of Texas MD Anderson Cancer Center /ID# 155263	Houston	Texas
United States	Carolina BioOncology Institute /ID# 155265	Huntersville	North Carolina
United States	The Angeles Clinic and Researc /ID# 156324	Los Angeles	California
United States	Tennessee Oncology-Nashville Centennial /ID# 158654	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Japan,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181	The MTD and the RPTD of ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 will be determined during the dose escalation phase of the study. Once the RPTD has been determined, the dose expansion portion will begin.	Up to 8 weeks
Primary	Time to Cmax (Tmax) of ABBV-927	Time to Cmax (Tmax) of ABBV-927.	Up to 12 weeks after participant's first dose
Primary	Maximum observed serum concentration (Cmax) of ABBV-927	Maximum observed serum concentration (Cmax) of ABBV-927.	Up to 12 weeks after participant's first dose
Primary	Terminal-Phase Elimination Rate Constant (ß) of ABBV-927	Terminal-phase elimination rate constant (ß)of ABBV-927.	Up to 12 weeks after participant's first dose
Primary	Terminal half-life (t1/2) of ABBV-927	Terminal half-life (t1/2) of ABBV-927.	Up to 4 weeks after participant's first dose
Primary	Area under the serum concentration-time curve (AUCt) of ABBV-927	Area under the serum concentration-time curve from time zero to the time of last measurable concentration (AUCt) of ABBV-927.	Up to 12 weeks after participant's first dose
Primary	Time to Cmax (Tmax) of ABBV-181	Time to Cmax (Tmax) of ABBV-181.	Up to 12 weeks after participant's first dose
Primary	Maximum observed serum concentration (Cmax) of ABBV-181	Maximum observed serum concentration (Cmax) of ABBV-181.	Up to 12 weeks after participant's first dose
Primary	Terminal-Phase Elimination Rate Constant (ß) of ABBV-181	Terminal-phase elimination rate constant (ß)of ABBV-181.	Up to 12 weeks after participant's first dose
Primary	Terminal half-life (t1/2) of ABBV-181	Terminal half-life (t1/2) of ABBV-181.	Up to 4 weeks after participant's first dose
Primary	Area under the serum concentration-time curve (AUCt) of ABBV-181	Area under the serum concentration-time curve from time zero to the time of last measurable concentration (AUCt) of ABBV-181.	Up to 12 weeks after participant's first dose
Primary	Number of Participants with Adverse Events	An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.	Up to 30 days after and up to 24-month of treatment period
Secondary	Clinical benefit rate (CBR, defined as the percentage of participants with a confirmed partial, complete response, or stable disease for at least 24 weeks to the treatment)	CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease for at least 24 weeks to the treatment.	Up to 30 days after and up to 24-month of treatment period
Secondary	Duration of objective response (DOR)	DOR is defined as the time from the initial objective response to disease progression or death, whichever occurs first.	Up to 30 days after and up to 24-month of treatment period
Secondary	Objective response rate (ORR)	ORR is defined as the proportion of participants with a confirmed partial or complete response to the treatment.	Up to 30 days after and up to 24-month of treatment period
Secondary	Progression-free survival (PFS)	PFS time is defined as the time from the first dose of ABBV-927 to disease progression or death, whichever occurs first.	Up to 30 days after and up to 24-month of treatment period