Study to Determine the Safety, Tolerability, Pharmacokinetics and Recommended Phase 2 Dose (RP2D) of ABBV-151 as a Single Agent and in Combination With ABBV-181 in Participants With Locally Advanced or Metastatic Solid Tumors

Sponsor

AbbVie (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03821935

Collaborator

(none)

260

Enrollment

Locations

Arms

56.3

Anticipated Duration (Months)

8.7

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study will determine the recommended Phase 2 dose (RP2D) of ABBV-151 administered as monotherapy and in combination with budigalimab (ABBV-181) as well as to assess the safety, pharmacokinetics (PK), and preliminary efficacy of ABBV-151 alone and in combination with budigalimab. The study will consist of 2 phases: dose escalation and dose expansion.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors Cancer	Drug: ABBV-151 Drug: Budigalimab	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

260 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 First-in Human, Multi-Center, Open Label Dose-Escalation Study to Determine the Safety, Tolerability, Pharmacokinetics and RP2D of ABBV-151 as a Single Agent and in Combination With ABBV-181 in Subjects With Locally Advanced or Metastatic Solid Tumors

Actual Study Start Date :

Feb 21, 2019

Anticipated Primary Completion Date :

Oct 31, 2023

Anticipated Study Completion Date :

Oct 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation: ABBV-151 Various doses of ABBV-151 administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).	Drug: ABBV-151 Liquid for intravenous infusion.
Experimental: Dose Escalation: ABBV-151 + Budigalimab Various doses of ABBV-151 + Budigalimab administered during dose escalation to determine the Recommended Phase 2 Dose (RP2D).	Drug: ABBV-151 Liquid for intravenous infusion. Drug: Budigalimab Lyophilized powder for solution for intravenous infusion. Other Names: ABBV-181
Experimental: Dose Expansion: ABBV-151 + Budigalimab Participants will receive ABBV-151 at the RP2D plus budigalimab Dose A administered Q4W.	Drug: ABBV-151 Liquid for intravenous infusion. Drug: Budigalimab Lyophilized powder for solution for intravenous infusion. Other Names: ABBV-181
Experimental: Biopsy Cohort: ABBV-151 Dose A Participants will receive ABBV-151 Dose A.	Drug: ABBV-151 Liquid for intravenous infusion.
Experimental: Biopsy Cohort: ABBV-151 Dose B Participants will receive ABBV-151 Dose B.	Drug: ABBV-151 Liquid for intravenous infusion.

Outcome Measures

Primary Outcome Measures

Dose Escalation: Recommended Phase 2 Dose (RP2D) ABBV-151 Monotherapy [Up to 28 days after the first dose of ABBV-151 monotherapy]
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation portion of the study.
Dose Escalation: RP2D ABBV-151 + Budigalimab Combination Therapy [Up to 28 days after the first dose of ABBV-151 and ABBV-181 combination therapy]
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the dose expansion arms, based on safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamic (PD) data collected during the dose escalation portion of the study.
Dose Expansion: Objective Response Rate (ORR) [Up to approximately 6 months after the first dose date of last participant in Dose Expansion]
ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary Outcome Measures

Dose Expansion: Duration of Response (DOR) [Up to approximately 6 months after the first dose date of last participant in Dose Expansion]
The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.
Dose Expansion: Progression-free Survival (PFS) [Up to approximately 6 months after the first dose date of last participant in Dose Expansion]
Progression-free survival is defined as the time from the participant's first dose of study treatment (ABBV-151 or ABBV-181) to the first date of either disease progression or death, whichever occurs first.
Maximum Observed Serum Concentration (Cmax) of ABBV-151 [Up to approximately 70 days after initial dose of study drug]
Maximum Serum Concentration (Cmax) of ABBV-151.
Time to Maximum Observed Serum Concentration (Tmax) of ABBV-151 [Up to approximately 70 days after initial dose of study drug]
Time to maximum serum concentration (Tmax) of ABBV-151.
Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCτ) of ABBV-151 [Up to approximately 70 days after initial dose of study drug]
Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCτ) of ABBV-151.
Terminal-phase Elimination Rate Constant (β) of ABBV-151 [Up to approximately 70 days after initial dose of study drug]
Apparent terminal phase elimination rate constant (β or Beta) of ABBV-151.
Terminal Phase Elimination Half-life (t1/2) of ABBV-151 [Up to approximately 70 days after initial dose of study drug]
Terminal phase elimination half-life (t1/2) of ABBV-151.
Maximum Observed Serum Concentration (Cmax) of Budigalimab [Up to approximately 70 days after initial dose of study drug]
Maximum Serum Concentration (Cmax) of budigalimab.
Time to Maximum Observed Serum Concentration (Tmax) of Budigalimab [Up to approximately 70 days after initial dose of study drug]
Time to maximum serum concentration (Tmax) of budigalimab.
Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCτ) of Budigalimab [Up to approximately 70 days after initial dose of study drug]
Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCτ) of budigalimab.
Terminal-phase Elimination Rate Constant (β) of Budigalimab [Up to approximately 70 days after initial dose of study drug]
Apparent terminal phase elimination rate constant (β or Beta) of budigalimab.
Terminal Phase Elimination Half-life (t1/2) of Budigalimab [Up to approximately 70 days after initial dose of study drug]
Terminal phase elimination half-life (t1/2) of budigalimab.
Number of Participants With Adverse Events (AEs) [Up to approximately 9 months after the first dose date of last participant]
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above.
Change in Vital Signs [Up to approximately 6 months after the first dose date of last participant]
Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.
Change in Laboratory Parameters [Up to approximately 6 months after the first dose date of last participant]
Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.
Change in Electrocardiogram (ECG) [Up to approximately 6 months after the first dose date of last participant]
12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.
Incidence of Anti-drug Antibody (ADA) [Up to approximately 6 months after the first dose date of last participant]
The number of participants with anti-drug antibodies.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

For Dose Escalation only: Participants with an advanced solid tumor who are considered refractory to or intolerant of all existing therapy(ies) known to provide a clinical benefit for their condition. Additionally, participants who have been offered standard therapies and refused, or who are considered ineligible for standard therapies, may be eligible for this study on a case-by-case basis, after discussion with and agreement from the sponsor. Participants with pancreatic adenocarcinoma, urothelial cancer, Hepatocellular carcinoma (HCC), or Head and neck squamous cell carcinoma (HNSCC) who are being considered for the dose escalation cohorts must also meet the histology specific eligibility criteria described below for dose expansion.
For Dose Expansion only participants must meet criteria specific to the type of cancer:
Pancreatic adenocarcinoma and have disease progression during or after 1 systemic therapy (gemcitabine monotherapy or in combination with other agents, FOLFIRINOX [or another regimen including both 5-fluorouracil and oxaliplatin], capecitabine monotherapy or in combination with other agents) administered in the adjuvant, locally advanced, or metastatic setting. If the therapy was used in an adjuvant setting, disease progression must have occurred within 6 months of completing adjuvant therapy.
Urothelial cancer of the bladder and urinary tract and must have progressed following treatment with a platinum-based regimen (administered in any line of therapy) and a programmed death 1/programmed death ligand 1 (PD1/PDL1) antagonist administered in the recurrent or metastatic setting (progression following a PD1/PDL1 antagonist is defined as unequivocal progression on or within 3 months of the last dose of anti-PD1 or anti-PDL1 therapy).
HCC and must have disease progression during or after 1 prior line of systemic therapy.
HNSCC (arising from the oral cavity, oropharynx, hypopharynx, or larynx) and must have progressed following treatment with platinum-based regimen (administered in any line of therapy) and a PD1/PDL1 antagonist administered in the recurrent or metastatic setting (progression following a PD1/PDL1 antagonist is defined as unequivocal progression on or within 3 months of the last dose of anti-PD1 or anti-PDL1 therapy).
CRC participants with microsatellite stable or mismatch repair proficient colorectal adenocarcinoma (as determined by PCR/NGS or IHC, respectively) who have received 1-2 prior chemotherapy regimens.
Participants with histologically or cytologically confirmed advanced or metastatic NSCLC who have received 1 prior line of chemotherapy and 1 prior anti-PD-(L)1 antibody, administered either concurrently or sequentially in the metastatic setting.
Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
Participant has adequate bone marrow, renal, hepatic, and coagulation function.
Must have a viral status consistent with the requirements described in the protocol specific to type of cancer and stage of study (Dose Escalation or Dose Expansion).

Exclusion Criteria:

For Dose Expansion only:
Participants with HCC, pancreatic adenocarcinoma, or microsatellite stable colorectal cancer (MSS-CRC) having prior exposure to a prior PD-1/PD-L1 antagonist in any line of therapy.
Participants (except for participants with urothelial cancer or HNSCC) who have had prior exposure to immunotherapies as listed in the protocol.
Has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, biologic, herbal therapy, or any investigational therapy within a period of 5 half-lives or 28 days (whichever is shorter), prior to the first dose of the study drug.
Participant has unresolved AEs > Grade 1 from prior anticancer therapy except for alopecia.
Has a history of primary immunodeficiency, bone marrow transplantation, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
Has a known uncontrolled metastases to the central nervous system (with certain exceptions).
Current or prior use of immunosuppressive medication within 14 days prior to the first dose of the study drug.
Has clinically significant uncontrolled condition(s).
History of inflammatory bowel disease, interstitial lung disease or pneumonitis, myocarditis, Stevens-Johnson syndrome, toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms (DRESS).
Live vaccine administration <= 28 days prior to the first dose of study drug.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale University /ID# 208356	New Haven	Connecticut	United States	06510
2	AdventHealth Celebration /ID# 224860	Celebration	Florida	United States	34747-4970
3	AdventHealth Cancer Institute - Orlando /ID# 226953	Orlando	Florida	United States	32804
4	Indiana Univ School Medicine /ID# 208384	Indianapolis	Indiana	United States	46202
5	Univ Michigan Med Ctr /ID# 221129	Ann Arbor	Michigan	United States	48109
6	NYU Langone Medical Center /ID# 209822	New York	New York	United States	10016-6402
7	Carolina BioOncology Institute /ID# 208358	Huntersville	North Carolina	United States	28078
8	The Ohio State University - The James /ID# 217611	Columbus	Ohio	United States	43210-1240
9	NEXT Oncology /ID# 208930	San Antonio	Texas	United States	78229
10	Chris O'Brien Lifehouse /ID# 213236	Camperdown	New South Wales	Australia	2050
11	Icon Cancer Centre /ID# 224961	South Brisbane	Queensland	Australia	4101
12	UCL Saint-Luc /ID# 218466	Woluwe-Saint-Lambert	Bruxelles-Capitale	Belgium	1200
13	Princess Margaret Cancer Centre /ID# 209423	Toronto	Ontario	Canada	M5G 2M9
14	CHU Toulouse - Hopital Purpan /ID# 218667	TOULOUSE Cedex 9	Haute-Garonne	France	31059
15	Centre Leon Berard /ID# 218515	Lyon CEDEX 08	Rhone	France	69373
16	Institut Gustave Roussy /ID# 218668	Villejuif Cedex	Val-de-Marne	France	94805
17	Centre Jean Perrin /ID# 218669	Clermont Ferrand		France	63011
18	The Chaim Sheba Medical Center /ID# 209037	Ramat Gan	Tel-Aviv	Israel	5265601
19	Tel Aviv Sourasky Medical Center /ID# 222199	Tel Aviv-Yafo	Tel-Aviv	Israel	6423906
20	Rambam Health Care Campus /ID# 222198	Haifa		Israel	3109601
21	National Cancer Center Hospital East /ID# 224808	Kashiwa-shi	Chiba	Japan	277-8577
22	National Cancer Center Hospital /ID# 209421	Chuo-ku	Tokyo	Japan	104-0045
23	Yonsei University Health System Severance Hospital /ID# 218512	Seoul	Seoul Teugbyeolsi	Korea, Republic of	03722
24	Seoul National University Hospital /ID# 218513	Seoul		Korea, Republic of	03080
25	Pan American Center for Oncology Trials, LLC /ID# 217475	Rio Piedras		Puerto Rico	00935
26	Hospital Clinic de Barcelona /ID# 221106	Barcelona		Spain	08036
27	Hospital Universitario Fundacion Jimenez Diaz /ID# 220928	Madrid		Spain	28040
28	Hospital Clinico Universitario de Valencia /ID# 221107	Valencia		Spain	46010
29	China Medical University Hospital /ID# 218492	Taichung City		Taiwan	40447
30	National Taiwan University Hospital /ID# 218490	Taipei City		Taiwan	100