A Study of Budigalimab (ABBV-181) in Participants With Advanced Solid Tumors

Advanced Solid Tumors Clinical Trial

Official title:

A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-181 as Monotherapy and in Combination With Another Anti-Cancer Therapy in Subjects With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03000257
• Other study ID #: M15-891
• Secondary ID: 2016-002520-89
• Status: Completed
• Phase: Phase 1
• Start date: December 14, 2016
• Est. completion date: March 29, 2022

Study information

• Verified date: April 2022
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 budigalimab. This study will also evaluate the safety and tolerability of budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with venetoclax. The study will consist of 3 parts: budigalimab monotherapy dose escalation and expansion, budigalimab in combination with Rovalpituzumab Tesirine and budigalimab in combination with venetoclax.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 182
• Est. completion date: March 29, 2022
• Est. primary completion date: March 29, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant must have an advanced solid tumor and must not be a candidate for surgical resection or other approved therapeutic regimen known to provide clinical benefit. For dose escalation, the participant may have been previously treated with a programmed cell death 1 (PD-I) targeting agent. For dose expansion, the participant must be PD-I/PD-L1 targeting agent naïve. For Part 2 budigalimab in combination with rovalpituzumab tesirine, the participant must have SCLC with progressive disease and have failed platinum containing therapy and be PD-1/PD-L1 targeting agent naïve. For Part 3 budigalimab in combination with venetoclax, the participant must have locally advanced or metastatic NSCLC and received 1 to 4 prior lines of therapy in the advanced or metastatic setting including 1 regimen that included a PD-1 or PD-L1 targeting agent which was discontinued following disease progression. Participants who are naïve to treatment with a PD-1/PD-L1 targeting agent OR who have received more than 1 regimen containing a PD-1/PD-L1 targeting agent are NOT eligible for Part 3.

• Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 for the monotherapy cohort and an ECOG 0 to 1 for budigalimab in combination with rovalpituzumab tesirine cohort (Part 2) and budigalimab in combination with venetoclax (Part 3).

• Participants have adequate bone marrow, renal, hepatic and coagulation function.

• Participants must have measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the dose escalation portion of the trial. Participants in the expansion cohort must have measurable disease per RECIST version 1.1 or disease evaluable by assessment of tumor antigens. Participants enrolled in budigalimab in combination with venetoclax cohort (Part 3) must have measurable disease per RECIST version 1.1.

Exclusion Criteria:

• Participant has received anticancer therapy including chemotherapy, immunotherapy, radiation therapy, biologic, small molecule, herbal therapy, or any investigational therapy within a period of 5 half-lives, prior to the first dose of budigalimab or Rovalpituzumab Tesirine or venetoclax.

• For budigalimab in combination with rovalpituzumab tesirine cohort (Part 2), participant must not have had prior exposure to Rovalpituzumab Tesirine or a pyrrolobenzodiazepine (PBD) based drug.

• Participant has unresolved adverse events greater than grade 1 from prior anticancer therapy except for alopecia.

• 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 A, B or C. Participants who have a history of hepatitis B or C who have undetectable hepatitis B (HBV) DNA or hepatitis C (HCV) RNA after anti-viral therapy may be enrolled.

• Participant has known history or inflammatory bowel disease, pneumonitis, or known uncontrolled metastases to the central nervous system (CNS) (with certain exceptions).

• Participants with a history of or ongoing pneumonitis or interstitial lung disease are also excluded.

• For budigalimab plus venetoclax therapy (Part 3), participant must not receive a strong or moderate inducer or inhibitor of cytochrome P450 (CYP)3A within 7 days before first venetoclax dose.

• For budigalimab plus venetoclax therapy (Part 3), participants with a known gastrointestinal disorder (i.e.: malabsorption syndrome), complication (i.e.: dysphagia) or surgery that could make consumption or absorption of oral medication problematic are also excluded.

• All Cohorts: Participants with a history of Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS)

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Drug:
• Venetoclax
Tablet taken orally
• Rovalpituzumab Tesirine
Intravenous infusion
• ABBV-181
Intravenous infusion

Locations

Country	Name	City	State
Australia	Blacktown Hospital /ID# 167386	Blacktown	New South Wales
Australia	St Vincent's Hospital Melbourne /ID# 167552	Fitzroy Melbourne	Victoria
Australia	Linear Clinical Research /ID# 170797	Nedlands	Western Australia
Austria	Medizinische Universitaet Graz /ID# 168752	Graz	Steiermark
Belgium	Universitair Ziekenhuis Antwerpen /ID# 170702	Edegem	Antwerpen
Belgium	UZ Gent /ID# 170881	Gent	Oost-Vlaanderen
Canada	Cross Cancer Institute /ID# 167603	Edmonton	Alberta
Finland	Docrates Cancer Center /ID# 166838	Helsinki
Finland	Tampere University Hospital /ID# 166839	Tampere	Pirkanmaa
France	Institut Bergonie /ID# 162662	Bordeaux	Gironde
France	Centre Leon Berard /ID# 162660	Lyon CEDEX 08	Rhone
France	Institut du Cancer de Montpellier - Val d'Aurelle /ID# 163999	Montpellier CEDEX 5	Herault
France	Institut Gustave Roussy /ID# 162753	Villejuif Cedex	Val-de-Marne
Japan	National Cancer Center Hospital /ID# 166279	Chuo-ku	Tokyo
Japan	National Hospital Organization Kyushu Cancer Center /ID# 206229	Fukuoka-shi	Fukuoka
Japan	National Cancer Center Hospital East /ID# 166433	Kashiwa-shi	Chiba
Spain	Hospital Universitario Fundacion Jimenez Diaz /ID# 163862	Madrid
Spain	Hospital Universitario HM Sanchinarro /ID# 163861	Madrid
Spain	Hospital Clinico Universitario de Valencia /ID# 163925	Valencia
Taiwan	National Taiwan University Hospital /ID# 163997	Taipei City
Taiwan	Taipei Medical University Hospital /ID# 163998	Taipei City
United States	The University of Chicago Medical Center /ID# 157375	Chicago	Illinois
United States	Virginia Cancer Specialists - Fairfax /ID# 157377	Fairfax	Virginia
United States	Carolina BioOncology Institute /ID# 157376	Huntersville	North Carolina
United States	Moores Cancer Center at UC San Diego /ID# 157374	La Jolla	California
United States	South Texas Accelerated Research Therapeutics /ID# 157378	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Finland,  France,  Japan,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Recommended Phase 2 Dose (RPTD) for Budigalimab	If a maximum tolerated dose (MTD) is reached, the RPTD of budigalimab 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 other available data.	Up to 6 months
Primary	Part 1: Maximum tolerated dose (MTD) of Budigalimab	MTD will be defined at the highest dose level at which less than 2 of 6 subjects or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity.	Up to 6 months
Primary	Part 1 and Part 3: Terminal Half-life (t1/2) of Budigalimab	Terminal phase elimination half-life (t1/2) of Budigalimab	Up to 4 Weeks
Primary	Part 1 and Part 3: Maximum Observed Serum Concentration (Cmax) of Budigalimab	Maximum Serum Concentration (Cmax) of Budigalimab	Up to 12 Weeks
Primary	Part 1 and Part 3: Time to Cmax (Tmax) of Budigalimab	Time to maximum plasma concentration of Budigalimab	Up to 12 Weeks
Primary	Part 1 and Part 3: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab	Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab	Up to 12 Weeks
Primary	Part 2: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Rovalpituzumab Tesirine Combination	The safety and tolerability of a single dose of Budigalimab in combination with Rovalpituzumab Tesirine will be assessed in patients with advanced small cell lung cancer (SCLC) to determine the RPTD and schedule for the combination.	Up to 6 Months
Primary	Part 3: Recommended Phase 2 Dose (RPTD) and Schedule for Budigalimab and Venetoclax Combination.	The safety and tolerability of Budigalimab in combination with venetoclax will be assessed in patients with metastatic Non-Small Cell Lung Cancer (NSCLC) to determine the RPTD for the combination.	Up to 6 Months
Primary	Part 3: Maximum Observed Serum Concentration (Cmax) for Venetoclax	Maximum Serum Concentration (Cmax) for Venetoclax	Up to 12 Weeks
Primary	Part 3: Area Under the Serum Concentration Time Curve from Time 0 to 24 Hours Post-dose (AUC(0-24)) of Venetoclax	Area Under the Plasma Concentration-time Curve from time 0 to time 0 to 24 hours post-dose (AUC(0-24)) of Venetoclax	Up to 12 Weeks
Primary	Part 3: Time to Cmax (Tmax) of Venetoclax	Time to maximum plasma concentration of of Venetoclax	Up to 12 Weeks
Primary	Part 1, Part 2, Part 3: Number of Participants with Adverse Events	An adverse event 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.	From first dose of study drug until 90 days following last dose of study drug (up to 24 months)
Secondary	Part 2: Terminal Half-life (t1/2) of Budigalimab	Terminal phase elimination half-life (t1/2) of Budigalimab	Up to 4 Weeks
Secondary	Part 2: Terminal Half-life (t1/2) of Rovalpituzumab Tesirine	Terminal phase elimination half-life (t1/2) of Rovalpituzumab Tesirine	Up to 4 Weeks
Secondary	Part 2: Maximum Observed Serum Concentration (Cmax) of Rovalpituzumab Tesirine	Maximum Serum Concentration (Cmax) of Rovalpituzumab Tesirine	Up to 12 Weeks
Secondary	Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Rovalpituzumab Tesirine	Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Rovalpituzumab Tesirine	Up to 12 Weeks
Secondary	Part 2: Area Under the Serum Concentration Time Curve from Time 0 to Last Measurable Concentration (AUCt) of Budigalimab	Area Under the Plasma Concentration-time Curve from time 0 to last measurable concentration (AUCt) of Budigalimab	Up to 12 Weeks
Secondary	Part 2: Time to Cmax (Tmax) of Budigalimab	Time to maximum plasma concentration of Budigalimab	Up to 12 Weeks
Secondary	Part 2: Time to Cmax (Tmax) of Rovalpituzumab Tesirine	Time to maximum plasma concentration of Rovalpituzumab Tesirine	Up to 12 Weeks
Secondary	Part 1 and Part 3: Objective response rate (ORR)	ORR is defined as the proportion of subjects with a confirmed partial or complete response to the treatment.	First dose of study drug through at least 30 days after last dose of study drug.
Secondary	Part 1 and Part 3: Clinical benefit rate (CBR, defined as CR, PR or SD)	CBR defined as the proportion of subjects with a confirmed partial response (PR), complete response (CR), or stable disease.	First dose of study drug through at least 30 days after last dose of study drug.
Secondary	Part 1 and Part 3: Progression-free survival (PFS)	PFS time is defined as the time from the participant's first dose of study drug (Day 1) to either the participant's disease progression or death, whichever occurs first.	First dose of study drug through at least 30 days after last dose of study drug.
Secondary	Part 1, Part 2 and Part 3: Duration of objective response (DOR)	DOR for a participant is defined as the time from the participant's initial objective response to study drug therapy to disease progression or death, whichever occurs first.	First dose of study drug through at least 30 days after last dose of study drug.