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

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

Sponsors

Lead Sponsor: AbbVie

Source AbbVie
Brief Summary

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

Overall Status Recruiting
Start Date February 21, 2019
Completion Date July 14, 2022
Primary Completion Date July 14, 2022
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Dose Escalation: Recommended Phase 2 Dose (RP2D) ABBV-151 Monotherapy Up to 28 days after the first dose of ABBV-151 monotherapy
Dose Escalation: RP2D ABBV-151 + ABBV-181 Combination Therapy Up to 28 days after the first dose of ABBV-151 and ABBV-181 combination therapy
Dose Expansion: Objective Response Rate (ORR) Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Secondary Outcome
Measure Time Frame
Dose Expansion: Duration of Response (DOR) Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Dose Expansion: Progression-free Survival (PFS) Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Maximum Observed Serum Concentration (Cmax) Up to approximately 70 days after initial dose of study drug
Time to Maximum Observed Serum Concentration (Tmax) Up to approximately 70 days after initial dose of study drug
Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCτ) Up to approximately 70 days after initial dose of study drug
Terminal-phase Elimination Rate Constant (β) Up to approximately 70 days after initial dose of study drug
Terminal Phase Elimination Half-life (t1/2) Up to approximately 70 days after initial dose of study drug
Enrollment 184
Condition
Intervention

Intervention Type: Drug

Intervention Name: ABBV-151

Description: liquid for intravenous infusion

Intervention Type: Drug

Intervention Name: ABBV-181

Description: lyophilized powder for solution for intravenous infusion

Arm Group Label: ABBV-151 + ABBV-181 Combination Therapy

Eligibility

Criteria:

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 triple-negative breast cancer (TNBC), 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:

- TNBC - Female or male participants with confirmed breast adenocarcinoma that is ER-negative, PR-negative, and HER2-negative, (as defined per American Society of Clinical Oncology [ASCO]/College of American Pathology [CAP] guidelines), who must have disease progression during or after at least 1 systemic therapy that included a taxane in the metastatic or recurrent setting.

- 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).

- 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 (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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
AbbVie Inc. Study Director AbbVie
Overall Contact

Last Name: ABBVIE CALL CENTER

Phone: 847.283.8955

Email: [email protected]

Location
Facility: Status:
Yale University /ID# 208356 | New Haven, Connecticut, 06510, United States Recruiting
Indiana Univ School Medicine /ID# 208384 | Indianapolis, Indiana, 46202, United States Recruiting
Univ Michigan Med Ctr /ID# 221129 | Ann Arbor, Michigan, 48109, United States Not yet recruiting
NYU Langone Medical Center /ID# 209822 | New York, New York, 10016-6402, United States Not yet recruiting
Carolina BioOncology Institute /ID# 208358 | Huntersville, North Carolina, 28078, United States Recruiting
The Ohio State University - The James /ID# 217611 | Columbus, Ohio, 43210-1240, United States Not yet recruiting
NEXT Oncology /ID# 208930 | San Antonio, Texas, 78229, United States Recruiting
Chris O'Brien Lifehouse /ID# 213236 | Camperdown, New South Wales, 2050, Australia Recruiting
Princess Margaret Cancer Centre /ID# 209423 | Toronto, Ontario, M5G 2M9, Canada Recruiting
Hopital Universitaire Purpan /ID# 218667 | Toulouse, Haute-Garonne, 31059, France Not yet recruiting
Centre Leon Berard /ID# 218515 | Lyon CEDEX 08, Rhone, 69373, France Not yet recruiting
Institut Gustave Roussy /ID# 218668 | Villejuif, Val-de-Marne, 94800, France Not yet recruiting
Rambam Health Care Campus /ID# 222198 | Haifa, 3109601, Israel Not yet recruiting
Sheba Medical Center /ID# 209037 | Ramat Gan, 5262100, Israel Recruiting
Tel Aviv Sourasky Medical Center /ID# 222199 | Tel Aviv-Yafo, 6423906, Israel Not yet recruiting
National Cancer Center Hospital /ID# 209421 | Chuo-ku, Tokyo, 104-0045, Japan Recruiting
Seoul National University Hospital /ID# 218513 | Seoul, 03080, Korea, Republic of Not yet recruiting
Severance Hospital /ID# 218512 | Seoul, 03722, Korea, Republic of Not yet recruiting
Hospital Clinic de Barcelona /ID# 221106 | Barcelona, 08036, Spain Not yet recruiting
Hospital Fundacion Jimenez Dia /ID# 220928 | Madrid, 28040, Spain Not yet recruiting
Hosp Clin Univ de Valencia /ID# 221107 | València, 46010, Spain Not yet recruiting
China Medical University Hosp /ID# 218492 | Taichung City, Taichung, 40447, Taiwan Not yet recruiting
National Taiwan University Hospital /ID# 218490 | Taipei City, Taipei, 100, Taiwan Not yet recruiting
Location Countries

Australia

Canada

France

Israel

Japan

Korea, Republic of

Spain

Taiwan

United States

Verification Date

June 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: ABBV-151 Monotherapy

Type: Experimental

Description: Various doses of ABBV-151 administered during dose escalation, followed by dose expansion of ABBV-151 administered at the Recommended Phase 2 Dose (RP2D).

Label: ABBV-151 + ABBV-181 Combination Therapy

Type: Experimental

Description: Various doses of ABBV-151 plus ABBV-181 Dose A administered every 4 weeks (Q4W) during dose escalation, followed by dose expansion of ABBV-151 administered at the RP2D plus ABBV-181 Dose A administered Q4W.

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention Model: Sequential Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov