A Study of ABBV-428, an Immunotherapy, in Subjects With Advanced Solid Tumors

Sponsor

AbbVie (Industry)

Overall Status

Completed

CT.gov ID

NCT02955251

Collaborator

(none)

Enrollment

Locations

Arms

35.3

Actual Duration (Months)

4.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is an open-label, Phase I, dose-escalation study to determine the recommended Phase 2 dose (RPTD), maximum tolerated dose (MTD), and evaluate the safety and pharmacokinetic (PK) profile of ABBV-428 when administered as monotherapy or in combination with nivolumab in participants with advanced solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors Cancer	Drug: ABBV-428 Drug: Nivolumab	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

61 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multi-Center, Phase 1, Open-Label, Dose-Escalation Study of ABBV-428, an Immunotherapy in Subjects With Advanced Solid Tumors

Actual Study Start Date :

Nov 18, 2016

Actual Primary Completion Date :

Oct 29, 2019

Actual Study Completion Date :

Oct 29, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 ABBV-428 will be administered at escalating dose levels in 28-day dosing cycles (2 doses per cycle).	Drug: ABBV-428 ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15.
Experimental: Arm A, B, and C Additional participants (with ovarian cancer, NSCLC, etc.) will be enrolled in a dose expansion cohorts that will further evaluate ABBV-428.	Drug: ABBV-428 ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15.
Experimental: Arm D Additional participants with NSCLC will be enrolled in an expansion cohort that will further evaluate ABBV-428 plus nivolumab.	Drug: ABBV-428 ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15. Drug: Nivolumab Nivolumab will be administered by intravenous infusion according to approved dose and dosing schedules. Other Names: OPDIVO
Experimental: Arm 2 ABBV-428 plus nivolumab.	Drug: ABBV-428 ABBV-428 will be administered by intravenous infusion in 28-day dosing cycles on Day 1 and Day 15. Drug: Nivolumab Nivolumab will be administered by intravenous infusion according to approved dose and dosing schedules. Other Names: OPDIVO

Outcome Measures

Primary Outcome Measures

Number of participants with adverse events [First dose of study drug through at least 100 days after end of treatment; up to 2 years after last participants first dose]
Recommended Phase 2 Dose (RPTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab [1 day of study drug administration within the 28-day cycle at the designated cohort dose]
If a maximum tolerated dose (MTD) is reached, the RPTD of ABBV-428 will not be a dose higher than the defined MTD, and will be selected based on the type(s) and occurrence(s) of dose limiting toxicities which occur in addition to the MTD. If a MTD is not reached, then the RPTD will be defined based on the safety and pharmacokinetic data.
Area under the serum concentration-time curve (AUC) of ABBV-428 [Up to 30 days after a 24-month treatment period]
Terminal half-life (t1/2) of ABBV-428 [Up to 30 days after a 24-month treatment period]
Maximum observed serum concentration (Cmax) of ABBV-428 [Up to 30 days after a 24-month treatment period]
Maximum tolerated dose (MTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab [Up to 2 years]
The highest dose level at which less than 2 of 6 participants or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity.
Time to Cmax (Tmax) of ABBV-428 [Up to 30 days after a 24-month treatment period]

Secondary Outcome Measures

Duration of Objective Response (DOR) [Up to 30 days after a 24-month of treatment period]
DOR defined as the time from the initial objective response to disease progression or death, whichever occurs first.
Clinical benefit rate (CBR) [Up to 30 days after a 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.
Progression-Free Survival (PFS) [Up to 30 days after a 24-month of treatment period]
PFS time is defined as the time from the first dose of ABBV-428 to disease progression or death, whichever occurs first
Objective Response Rate (ORR) [Up to 30 days after a 24-month of treatment period]
ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants 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 have adequate bone marrow, renal, hepatic and coagulation function.
For all dose expansion arms, participants must have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Participants in combination therapy cohorts must have an advanced solid tumor where the use of nivolumab is standard therapy.

Exclusion Criteria:

Active or prior documented autoimmune disease in the last 2 years. Participants with childhood atopy or asthma, vitiligo, alopecia, Hashimoto syndrome, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
Current or prior use of immunosuppressive medication within 14 days prior to the first dose (with certain exceptions).
History of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic leukemia, solid organ transplantation, or previous clinical diagnosis of tuberculosis.
Confirmed positive test results for human immunodeficiency virus (HIV), or participants with chronic or active hepatitis B or C. Participants who have a history of hepatitis B or C who have undetectable HBV DNA or HCV RNA after anti-viral therapy may be enrolled.
Prior grade greater than or equal to 3 immune-mediated neurotoxicity or pneumonitis (or any other unresolved or symptomatic adverse event in the last 3 months) while receiving immunotherapy.
Male participants who are 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	HonorHealth Research Institute - Pima /ID# 155461	Scottsdale	Arizona	United States	85258-2345
2	UC Davis Comprehensive Cancer Center - Main /ID# 154439	Sacramento	California	United States	95817
3	University of Chicago /ID# 154440	Chicago	Illinois	United States	60637-1443
4	Fox Chase Cancer Center /ID# 170665	Philadelphia	Pennsylvania	United States	19111
5	Greenville Hospital System /ID# 154437	Greenville	South Carolina	United States	29605
6	MD Anderson Cancer Center at Texas Medical Center /ID# 154441	Houston	Texas	United States	77030-4000
7	South Texas Accelerated Research Therapeutics /ID# 154442	San Antonio	Texas	United States	78229
8	Chris O'Brien Lifehouse /ID# 163131	Camperdown	New South Wales	Australia	2050
9	Northern Cancer Institute /ID# 163132	St Leonards	New South Wales	Australia	2065
10	Institut Bergonie /ID# 202391	Bordeaux	Gironde	France	33000
11	Institut Curie /ID# 162258	Paris CEDEX 05	Ile-de-France	France	75248
12	Gustave Roussy /ID# 162257	Villejuif	Ile-de-France	France	94805
13	Hopital de la Timone /ID# 162256	Marseille CEDEX 05	Provence-Alpes-Cote-d Azur	France	13385
14	Centre Leon Berard /ID# 168072	Lyon CEDEX 08	Rhone	France	69373
15	National Taiwan Univ Hosp /ID# 169034	Taipei City	Taipei	Taiwan	10002