Clinical trial NCT03821935: 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
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors Cancer
Keywords: Advanced Solid Tumors Cancer
cancer
Solid Tumors
metastatic
monotherapy
combination therapy
triple negative breast cancer (TNBC)
pancreatic adenocarcinoma
urothelial cancer
hepatocellular carcinoma (HCC)
head and neck squamous cell carcinoma (HNSCC)
Colorectal cancer
Ovarian granulosa cell tumors
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2019-01-30
Enrollment: 364
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.


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 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.

Primary outcomes:
measure: Dose Escalation: Recommended Phase 2 Dose (RP2D) Livmoniplimab Monotherapy
timeFrame: Up to 28 days after the first dose of Livmoniplimab monotherapy
measure: Dose Escalation: RP2D Livmoniplimab + Budigalimab Combination Therapy
timeFrame: Up to 28 days after the first dose of Livmoniplimab and Budigalimab combination therapy
measure: Dose Expansion: Objective Response Rate (ORR)
timeFrame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion
Secondary outcomes:
measure: Dose Expansion: Duration of Response (DOR)
timeFrame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion
measure: Dose Expansion: Progression-free Survival (PFS)
timeFrame: Up to approximately 6 months after the first dose date of last participant in Dose Expansion
measure: Maximum Observed Serum Concentration (Cmax) of Livmoniplimab
timeFrame: Up to approximately 70 days after initial dose of study drug
measure: Time to Maximum Observed Serum Concentration (Tmax) of Livmoniplimab
timeFrame: Up to approximately 70 days after initial dose of study drug
measure: Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCτ) of Livmoniplimab
timeFrame: Up to approximately 70 days after initial dose of study drug
measure: Terminal-phase Elimination Rate Constant (β) of Livmoniplimab
timeFrame: Up to approximately 70 days after initial dose of study drug
measure: Terminal Phase Elimination Half-life (t1/2) of Livmoniplimab
timeFrame: Up to approximately 70 days after initial dose of study drug
measure: Maximum Observed Serum Concentration (Cmax) of Budigalimab
timeFrame: Up to approximately 70 days after initial dose of study drug
measure: Time to Maximum Observed Serum Concentration (Tmax) of Budigalimab
timeFrame: Up to approximately 70 days after initial dose of study drug
measure: Area Under the Plasma Concentration-time Curve over time from 0 to last measurable concentration (AUCτ) of Budigalimab
timeFrame: Up to approximately 70 days after initial dose of study drug
measure: Terminal-phase Elimination Rate Constant (β) of Budigalimab
timeFrame: Up to approximately 70 days after initial dose of study drug
measure: Terminal Phase Elimination Half-life (t1/2) of Budigalimab
timeFrame: Up to approximately 70 days after initial dose of study drug
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 9 months after the first dose date of last participant
measure: Change in Vital Signs
timeFrame: Up to approximately 6 months after the first dose date of last participant
measure: Change in Laboratory Parameters
timeFrame: Up to approximately 6 months after the first dose date of last participant
measure: Change in Electrocardiogram (ECG)
timeFrame: Up to approximately 6 months after the first dose date of last participant
measure: Incidence of Anti-drug Antibody (ADA)
timeFrame: Up to approximately 6 months after the first dose date of last participant
measure: Dose Expansion Cohorts 10 to 12: Overall Survival (OS)
timeFrame: Up to approximately 6 months after the first dose date of last participant in Cohorts 10 to 12
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology Group, PA /ID# 218942
state: Arkansas
city: Duarte
country: United States
facility: City of Hope National Medical Center /ID# 265620
state: California
city: Irvine
country: United States
facility: City of Hope Orange County Lennar Foundation Cancer Center /ID# 270785
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine /ID# 208356
state: Connecticut
city: Celebration
country: United States
facility: AdventHealth Celebration /ID# 224860
state: Florida
city: Orlando
country: United States
facility: Duplicate_AdventHealth Cancer Institute - Orlando /ID# 226953
state: Florida
city: Indianapolis
country: United States
facility: Indiana Univ School Medicine /ID# 208384
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network, Inc. /ID# 257032
state: Indiana
city: Ann Arbor
country: United States
facility: Univ Michigan Med Ctr /ID# 221129
state: Michigan
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 259684
state: Missouri
city: Billings
country: United States
facility: Intermountain Health West End Clinic Gynecologic Oncology /ID# 266171
state: Montana
city: New York
country: United States
facility: NYU Langone Medical Center /ID# 209822
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai /ID# 264653
state: New York
city: Huntersville
country: United States
facility: Carolina BioOncology Institute /ID# 208358
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University - The James /ID# 217611
state: Ohio
city: Oklahoma City
country: United States
facility: Ou Health - Stephenson Cancer Center /ID# 268826
state: Oklahoma
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (SMO/Network/Consortium) /ID# 264900
state: Tennessee
city: El Paso
country: United States
facility: Renovatio clinical /ID# 265109
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology /ID# 208930
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical /ID# 265054
state: Texas
city: Seattle
country: United States
facility: University of Washington Medical Center /ID# 268854
state: Washington
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse /ID# 213236
state: New South Wales
city: South Brisbane
country: Australia
facility: Icon Cancer Centre /ID# 224961
state: Queensland
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires UCL Saint-Luc /ID# 218466
state: Bruxelles-Capitale
city: Toronto
country: Canada
facility: University Health Network_Princess Margaret Cancer Centre /ID# 209423
state: Ontario
city: TOULOUSE Cedex 9
country: France
facility: CHU Toulouse - Hopital Purpan /ID# 218667
state: Haute-Garonne
city: Lyon CEDEX 08
country: France
facility: Centre Leon Berard /ID# 218515
state: Rhone
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy /ID# 218668
state: Val-de-Marne
city: Clermont Ferrand
country: France
facility: Centre Jean Perrin /ID# 218669
city: Essen
country: Germany
facility: Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung /ID# 269587
state: Nordrhein-Westfalen
city: Haifa
country: Israel
facility: Rambam Health Care Campus /ID# 222198
state: H_efa
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 209037
state: Tel-Aviv
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center /ID# 222199
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Hebrew University /ID# 257918
city: Petah Tikva
country: Israel
facility: Rabin Medical Center /ID# 258479
city: Milan
country: Italy
facility: Istituto Europeo Di Oncologia /Id# 266053
state: Milano
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 224808
state: Chiba
city: Akashi-shi
country: Japan
facility: Hyogo Cancer Center /ID# 272553
state: Hyogo
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital /ID# 209421
state: Tokyo
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center /ID# 257572
state: Gyeonggido
city: Hwasun-gun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital /ID# 257573
state: Jeonranamdo
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital /ID# 257574
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 218513
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 266799
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center /ID# 265865
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital /ID# 218512
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki /ID# 266324
state: Lodzkie
city: Krakow
country: Poland
facility: Jagiellonskie Centrum Innowacji Sp. z o.o. /ID# 266194
state: Malopolskie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Bada /ID# 266147
state: Mazowieckie
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials, LLC /ID# 217475
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona /ID# 266632
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron /ID# 265290
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona /ID# 221106
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra - Madrid /ID# 265299
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal /ID# 265298
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz /ID# 220928
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro /ID# 265294
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia /ID# 221107
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital /ID# 265560
state: Kaohsiung
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 218490
state: Taipei
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 257634
city: Taichung
country: Taiwan
facility: China Medical University Hospital /ID# 218492
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hosp /ID# 257635
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital /ID# 265551
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: