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

Sponsor

AbbVie (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02988960

Collaborator

(none)

163

Enrollment

Locations

Arms

68.1

Anticipated Duration (Months)

7.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors Cancer	Drug: ABBV-927 Drug: ABBV-927 Drug: ABBV-181	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

163 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Feb 22, 2017

Anticipated Primary Completion Date :

Oct 27, 2022

Anticipated Study Completion Date :

Oct 27, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Escalating Arm 1: ABBV-927 Participants with solid tumors will receive escalating intravenous (IV) doses of ABBV-927.	Drug: ABBV-927 Intravenous
Experimental: Escalating Arm 2: ABBV-927 Participants with solid tumors will receive escalating intratumoral (IT) doses of ABBV-927.	Drug: ABBV-927 Intratumoral
Experimental: Escalating Arm 3: ABBV-927+ABBV-181 Participants with Non-Small Cell Lung Cancer (NSCLC) will receive escalating IV doses of ABBV-927 and IV doses of ABBV-181.	Drug: ABBV-927 Intravenous Drug: ABBV-181 Intravenous Other Names: Budigalimab
Experimental: Escalating Arm 4: ABBV-927+ABBV-181 Participants with Head and Neck Squamous Cell Carcinoma (HNSCC) will receive escalating IT doses of ABBV-927 and IV doses of ABBV-181.	Drug: ABBV-927 Intratumoral Drug: ABBV-181 Intravenous Other Names: Budigalimab
Experimental: Escalating Arm 5 (Japan): ABBV-927 Participants with solid tumors will receive escalating intravenous (IV) doses of ABBV-927.	Drug: ABBV-927 Intravenous
Experimental: Escalating Arm 6 (Japan): ABBV-927+ABBV-181 Participants with solid tumors will receive escalating IV doses of ABBV-927 and IV doses of ABBV-181.	Drug: ABBV-927 Intravenous Drug: ABBV-181 Intravenous Other Names: Budigalimab
Experimental: Expansion Arm A: ABBV-927 Additional participants with HNSCC or NSCLC will receive intravenous (IV) doses of ABBV-927.	Drug: ABBV-927 Intravenous
Experimental: Expansion Arm B: ABBV-927+ABBV-181 Additional participants with HNSCC will receive IT doses of ABBV-927 and IV doses of ABBV-181.	Drug: ABBV-927 Intratumoral Drug: ABBV-181 Intravenous Other Names: Budigalimab
Experimental: Expansion Arm C: ABBV-927+ABBV-181 Additional participants with NSCLC will receive IV doses of ABBV-927 and IV doses of ABBV-181.	Drug: ABBV-927 Intravenous Drug: ABBV-181 Intravenous Other Names: Budigalimab

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose (MTD) or recommended Phase 2 dose (RPTD) for ABBV-927 when administered as monotherapy or as combination therapy with ABBV-181 [Up to 8 weeks]
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.
Time to Cmax (Tmax) of ABBV-927 [Up to 12 weeks after participant's first dose]
Time to Cmax (Tmax) of ABBV-927.
Maximum observed serum concentration (Cmax) of ABBV-927 [Up to 12 weeks after participant's first dose]
Maximum observed serum concentration (Cmax) of ABBV-927.
Terminal-Phase Elimination Rate Constant (β) of ABBV-927 [Up to 12 weeks after participant's first dose]
Terminal-phase elimination rate constant (β)of ABBV-927.
Terminal half-life (t1/2) of ABBV-927 [Up to 4 weeks after participant's first dose]
Terminal half-life (t1/2) of ABBV-927.
Area under the serum concentration-time curve (AUCt) of ABBV-927 [Up to 12 weeks after participant's first dose]
Area under the serum concentration-time curve from time zero to the time of last measurable concentration (AUCt) of ABBV-927.
Time to Cmax (Tmax) of ABBV-181 [Up to 12 weeks after participant's first dose]
Time to Cmax (Tmax) of ABBV-181.
Maximum observed serum concentration (Cmax) of ABBV-181 [Up to 12 weeks after participant's first dose]
Maximum observed serum concentration (Cmax) of ABBV-181.
Terminal-Phase Elimination Rate Constant (β) of ABBV-181 [Up to 12 weeks after participant's first dose]
Terminal-phase elimination rate constant (β)of ABBV-181.
Terminal half-life (t1/2) of ABBV-181 [Up to 4 weeks after participant's first dose]
Terminal half-life (t1/2) of ABBV-181.
Area under the serum concentration-time curve (AUCt) of ABBV-181 [Up to 12 weeks after participant's first dose]
Area under the serum concentration-time curve from time zero to the time of last measurable concentration (AUCt) of ABBV-181.
Number of Participants with Adverse Events [Up to 30 days after and up to 24-month of treatment period]
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.

Secondary Outcome Measures

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) [Up to 30 days after and up to 24-month of treatment period]
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.
Duration of objective response (DOR) [Up to 30 days after and up to 24-month of treatment period]
DOR is defined as the time from the initial objective response to disease progression or death, whichever occurs first.
Objective response rate (ORR) [Up to 30 days after and up to 24-month of treatment period]
ORR is defined as the proportion of participants with a confirmed partial or complete response to the treatment.
Progression-free survival (PFS) [Up to 30 days after and up to 24-month of treatment period]
PFS time is defined as the time from the first dose of ABBV-927 to disease progression or death, whichever occurs first.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Angeles Clinic and Researc /ID# 156324	Los Angeles	California	United States	90025
2	The University of Chicago Medical Center /ID# 155264	Chicago	Illinois	United States	60637-1443
3	Massachusetts General Hospital /ID# 155267	Boston	Massachusetts	United States	02114
4	Carolina BioOncology Institute /ID# 155265	Huntersville	North Carolina	United States	28078
5	Tennessee Oncology-Nashville Centennial /ID# 158654	Nashville	Tennessee	United States	37203-1632
6	University of Texas MD Anderson Cancer Center /ID# 155263	Houston	Texas	United States	77030
7	Virginia Cancer Specialists - Fairfax /ID# 155266	Fairfax	Virginia	United States	22031
8	Peninsula Oncology Centre /ID# 164372	Frankston	Victoria	Australia	3199
9	Austin Health /ID# 171189	Heidelberg	Victoria	Australia	3084
10	Princess Margaret Cancer Centre /ID# 200819	Toronto	Ontario	Canada	M5G 2M9
11	Institut Bergonie /ID# 162665	Bordeaux	Gironde	France	33000
12	Duplicate_Institut Regional du Cancer /ID# 163609	Montpellier CEDEX 5	Herault	France	34298
13	Centre Leon Berard /ID# 162663	Lyon CEDEX 08	Rhone	France	69373
14	Institut Gustave Roussy /ID# 162666	Villejuif Cedex	Val-de-Marne	France	94805
15	National Cancer Center Hospital East /ID# 216870	Kashiwa-shi	Chiba	Japan	277-8577
16	National Cancer Center Hospital /ID# 217758	Chuo-ku	Tokyo	Japan	104-0045
17	Yonsei University Health System Severance Hospital /ID# 166292	Seoul	Seoul Teugbyeolsi	Korea, Republic of	03722
18	Seoul National University Hospital /ID# 166291	Seoul		Korea, Republic of	03080
19	Hospital Universitario Puerta de Hierro, Majadahonda /ID# 200129	Majadahonda	Madrid	Spain	28222
20	Hospital Universitario Fundacion Jimenez Diaz /ID# 200128	Madrid		Spain	28040
21	Hospital Universitario HM Sanchinarro /ID# 200127	Madrid		Spain	28050
22	Hospital Universitario y Politecnico La Fe /ID# 200975	Valencia		Spain	46026