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

Advanced Solid Tumors Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03821935
• Other study ID #: M19-345
• Secondary ID: 2023-508281-15-0
• Status: Recruiting
• Phase: Phase 1
• Start date: February 21, 2019
• Est. completion date: June 23, 2027

Study information

• Verified date: April 2024
• Source: AbbVie
• Contact: ABBVIE CALL CENTER
• Phone: 844-663-3742
• Email: abbvieclinicaltrials[@]abbvie.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 362
• Est. completion date: June 23, 2027
• Est. primary completion date: June 23, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (UC), 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.
• UC of the bladder and urinary tract and must have progressed following treatment

with:

• Cohort 4: 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).
• Cohort 11: One or more prior line of therapy in the locally advanced or metastatic setting. Participant must have experienced radiographic progression or relapse during or after a CPI (anti-PD1 or anti-PD-L1) for locally advanced or metastatic disease.
• 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).
• Microsatellite stable colorectal cancer (MSS-CRC) [unselected] participants with microsatellite stable or mismatch repair proficient colorectal adenocarcinoma (as determined by polymerase chain reaction (PCR)/Next-Generation sequencing (NGS) or immunohistochemistry (IHC), respectively) who have received 1-2 prior chemotherapy regimens.
• Non-small cell lung cancer (NSCLC) relapsed/refractory (R/R): 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.
• MSS-CRC (CMS4 enriched): Participants with microsatellite stable or mismatch repair proficient colorectal adenocarcinoma who have received prior fluorouracil-based combination chemotherapy regimens including oxaliplatin and irinotecan (with or without VEGF and/or EGFR targeted agents) and with a CMS4 subtype as determined by NGS of tumor biopsies. Archival tissue must be submitted for assessment of CMS4 subtype status during prescreening. Participants must have progressed on or refused available standard of care therapies. Additionally, participant who are considered not appropriate or ineligible for available standard of care therapies per investigator assessment will be eligible for this study.
• Ovarian granulosa (OG) cell tumor: Participants with histologically confirmed advanced nonresectable or metastatic adult granulosa cell tumor of the ovary that is not amenable to curative intent surgery or radiation. Additionally, there is documentation of radiological evidence of relapse after at least 1 line of systemic chemotherapy.
• 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 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.

Related Conditions & MeSH terms

• Advanced Solid Tumors Cancer
• Neoplasms

Intervention

Drug:
• Livmoniplimab
Liquid for intravenous infusion.
• Budigalimab
Lyophilized powder for solution for intravenous infusion.

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse /ID# 213236	Camperdown	New South Wales
Australia	Icon Cancer Centre /ID# 224961	South Brisbane	Queensland
Belgium	Cliniques Universitaires UCL Saint-Luc /ID# 218466	Woluwe-Saint-Lambert	Bruxelles-Capitale
Canada	Princess Margaret Cancer Centre /ID# 209423	Toronto	Ontario
France	Centre Jean Perrin /ID# 218669	Clermont Ferrand
France	Centre Leon Berard /ID# 218515	Lyon CEDEX 08	Rhone
France	CHU Toulouse - Hopital Purpan /ID# 218667	TOULOUSE Cedex 9	Haute-Garonne
France	Institut Gustave Roussy /ID# 218668	Villejuif Cedex	Val-de-Marne
Israel	Rabin Medical Center /ID# 258479	Haifa
Israel	Rambam Health Care Campus /ID# 222198	Haifa	H_efa
Israel	Hadassah Medical Center-Hebrew University /ID# 257918	Jerusalem
Israel	The Chaim Sheba Medical Center /ID# 209037	Ramat Gan	Tel-Aviv
Israel	Tel Aviv Sourasky Medical Center /ID# 222199	Tel Aviv	Tel-Aviv
Japan	National Cancer Center Hospital /ID# 209421	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East /ID# 224808	Kashiwa-shi	Chiba
Korea, Republic of	Chonnam National University Hwasun Hospital /ID# 257573	Hwasun-gun	Jeonranamdo
Korea, Republic of	Gachon University Gil Medical Center /ID# 257572	Incheon	Gyeonggido
Korea, Republic of	Korea University Anam Hospital /ID# 257574	Seoul
Korea, Republic of	Seoul National University Hospital /ID# 218513	Seoul
Korea, Republic of	Yonsei University Health System Severance Hospital /ID# 218512	Seoul	Seoul Teugbyeolsi
Puerto Rico	Pan American Center for Oncology Trials, LLC /ID# 217475	Rio Piedras
Spain	Hospital Clinic de Barcelona /ID# 221106	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Diaz /ID# 220928	Madrid
Spain	Hospital Clinico Universitario de Valencia /ID# 221107	Valencia
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 257634	Kaohsiung
Taiwan	China Medical University Hospital /ID# 218492	Taichung
Taiwan	Taipei Veterans General Hosp /ID# 257635	Taipei
Taiwan	National Taiwan University Hospital /ID# 218490	Taipei City
United States	Univ Michigan Med Ctr /ID# 221129	Ann Arbor	Michigan
United States	AdventHealth Celebration /ID# 224860	Celebration	Florida
United States	The Ohio State University - The James /ID# 217611	Columbus	Ohio
United States	Carolina BioOncology Institute /ID# 208358	Huntersville	North Carolina
United States	Community Health Network, Inc. /ID# 257032	Indianapolis	Indiana
United States	Indiana Univ School Medicine /ID# 208384	Indianapolis	Indiana
United States	Yale University School of Medicine /ID# 208356	New Haven	Connecticut
United States	NYU Langone Medical Center /ID# 209822	New York	New York
United States	Duplicate_AdventHealth Cancer Institute - Orlando /ID# 226953	Orlando	Florida
United States	Washington University-School of Medicine /ID# 259684	Saint Louis	Missouri
United States	NEXT Oncology /ID# 208930	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Israel,  Japan,  Korea, Republic of,  Puerto Rico,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Escalation: Recommended Phase 2 Dose (RP2D) Livmoniplimab 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.	Up to 28 days after the first dose of Livmoniplimab monotherapy
Primary	Dose Escalation: RP2D Livmoniplimab + Budigalimab 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.	Up to 28 days after the first dose of Livmoniplimab and Budigalimab combination therapy
Primary	Dose Expansion: Objective Response Rate (ORR)	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.	Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Secondary	Dose Expansion: Duration of Response (DOR)	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.	Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Secondary	Dose Expansion: Progression-free Survival (PFS)	Progression-free survival is defined as the time from the participant's first dose of study treatment (livmoniplimab or budigalimab) to the first date of either disease progression or death, whichever occurs first.	Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Secondary	Maximum Observed Serum Concentration (Cmax) of Livmoniplimab	Maximum Serum Concentration (Cmax) of livmoniplimab.	Up to approximately 70 days after initial dose of study drug
Secondary	Time to Maximum Observed Serum Concentration (Tmax) of Livmoniplimab	Time to maximum serum concentration (Tmax) of livmoniplimab.	Up to approximately 70 days after initial dose of study drug
Secondary	Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCt) of Livmoniplimab	Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCt) of livmoniplimab.	Up to approximately 70 days after initial dose of study drug
Secondary	Terminal-phase Elimination Rate Constant (ß) of Livmoniplimab	Apparent terminal phase elimination rate constant (ß or Beta) of livmoniplimab.	Up to approximately 70 days after initial dose of study drug
Secondary	Terminal Phase Elimination Half-life (t1/2) of Livmoniplimab	Terminal phase elimination half-life (t1/2) of livmoniplimab.	Up to approximately 70 days after initial dose of study drug
Secondary	Maximum Observed Serum Concentration (Cmax) of Budigalimab	Maximum Serum Concentration (Cmax) of budigalimab.	Up to approximately 70 days after initial dose of study drug
Secondary	Time to Maximum Observed Serum Concentration (Tmax) of Budigalimab	Time to maximum serum concentration (Tmax) of budigalimab.	Up to approximately 70 days after initial dose of study drug
Secondary	Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCt) of Budigalimab	Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration (AUCt) of budigalimab.	Up to approximately 70 days after initial dose of study drug
Secondary	Terminal-phase Elimination Rate Constant (ß) of Budigalimab	Apparent terminal phase elimination rate constant (ß or Beta) of budigalimab.	Up to approximately 70 days after initial dose of study drug
Secondary	Terminal Phase Elimination Half-life (t1/2) of Budigalimab	Terminal phase elimination half-life (t1/2) of budigalimab.	Up to approximately 70 days after initial dose of study drug
Secondary	Number of Participants With Adverse Events (AEs)	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.	Up to approximately 9 months after the first dose date of last participant
Secondary	Change in Vital Signs	Number of participants with clinically significant change from baseline in vital signs like systolic and diastolic blood pressure will be reported.	Up to approximately 6 months after the first dose date of last participant
Secondary	Change in Laboratory Parameters	Number of participants with clinically significant change from baseline in clinical laboratory test results like hematology will be reported.	Up to approximately 6 months after the first dose date of last participant
Secondary	Change in Electrocardiogram (ECG)	12-lead resting ECGs will be recorded. Parameters include RR interval, PR interval, QT interval, and QRS duration.	Up to approximately 6 months after the first dose date of last participant
Secondary	Incidence of Anti-drug Antibody (ADA)	The number of participants with anti-drug antibodies.	Up to approximately 6 months after the first dose date of last participant
Secondary	Dose Expansion Cohorts 10 to 12: Overall Survival (OS)	OS is defined as time from first study treatment to death due to any cause.	Up to approximately 6 months after the first dose date of last participant in Cohorts 10 to 12

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