Clinical trial NCT06632951: Study to Evaluate Adverse Events and Change in Disease Activity When Intravenously (IV) Infused Livmoniplimab is Used in Combination With IV Infused Budigalimab in Adult Participants With Urothelial Carcinoma (UC)
Official title: A Phase 2, Open-Label, Randomized Study of Livmoniplimab in Combination With Budigalimab Versus Chemotherapy in Subjects With Metastatic Urothelial Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Urothelial Carcinoma
Keywords: Urothelial Carcinoma
Metastatic Urothelial Carcinoma
Docetaxel
Paclitaxel
Gemcitabine
Livmoniplimab
Budigalimab
ABBV-181
ABBV-151
Cancer
LIVIGNO-3
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2024-10-09
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Urothelial carcinoma (UC) is the ninth most common cancer type worldwide. While the treatment of front-line metastatic urothelial carcinoma (mUC) has improved, there remains a high unmet need for effective therapies for participants who have recurrent disease and disease that has progressed after frontline treatment. The purpose of this study is to evaluate the optimized dose, adverse events, and efficacy of livmoniplimab in combination with budigalimab.

Livmoniplimab is an investigational drug being developed for the treatment of mUC. There are 3 treatment arms in this study and participants will be randomized in a 1:1:1 ratio. Participants will either receive livmoniplimab (at one of 2 different doses) in combination with budigalimab (another investigational drug), or either docetaxel, paclitaxel, or gemcitabine (based on investigator's choice). Approximately 150 adult participants will be enrolled in the study across 56 sites worldwide.

In arm 1, participants will receive intravenously (IV) infused livmoniplimab (dose A) in combination with IV infused budigalimab. In arm 2, participants will receive IV infused livmoniplimab (dose B) in combination with IV infused budigalimab. In arm 3 (control), participants will receive the investigator's choice: IV infused or injected docetaxel; IV infused or injected paclitaxel; or IV infused gemcitabine. The estimated duration of the study is up to approximately 3.5 years.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, questionnaires, and scans.


Eligibility criteria: Inclusion Criteria:

* Participant has histologically or cytologically confirmed urothelial carcinoma (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Mixed histologic types are allowed if urothelial (transitional cell) is the predominant histology.
* Participant has radiologically documented metastatic disease.
* Participant must have experienced radiographic progression or relapse on checkpoint inhibitor (anti-programmed cell death protein 1 \[PD-1\] or anti-programmed death-ligand 1 \[PD-L1\]) in the metastatic, adjuvant, or neo-adjuvant setting. Participant must have received at least 2 cycles of anti-PD-1 or anti-PD-L1.
* Participants eligible for platinum must have received a platinum containing regimen (cisplatin or carboplatin) in the metastatic, locally advanced, neoadjuvant, or adjuvant setting. If platinum was administered in the neoadjuvant or adjuvant setting, participant must have progressed within 6 months of completion of treatment. Platinum ineligible participants may enroll in this study without receiving a platinum containing regimen.
* Participant has at least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) v1.1 as determined by investigator.
* Life expectancy must be at least 3 months.

Exclusion Criteria:

* Participant has received more than 1 prior chemotherapy regimen for urothelial cancer in metastatic setting, including chemotherapy agents planned in comparator arm.

  * Platinum based chemotherapy administered in adjuvant or neoadjuvant setting will count towards this criterion if participant progressed within 6 months of completion.
  * Chemotherapy administered during concurrent chemoradiotherapy for primary cancer will not count towards this criterion.
  * The substitution of carboplatin for cisplatin does not constitute a new regimen provided no new chemotherapeutic agents were added to the regimen and no progression was noted prior to the change in platinum.
  * Antibody-drug conjugate (ADC) will not count towards this criterion.
  * Participant who previously received gemcitabine in combination with platinum in metastatic setting will be eligible to receive docetaxel or paclitaxel in comparator arm.
* Participant has received more than 1 antibody-drug conjugate (ADC) in metastatic setting.
* Has had prior radiation therapy within 28 days prior to first dose of study drug or who has not recovered (i.e., \<= Grade 1 or at baseline) from adverse events due to radiotherapy.
* History of additional malignancy or history of prior malignancy, except for adequately treated basal or squamous skin cancer, or cervical carcinoma in situ without evidence of disease, or malignancy treated with curative intent and with no evidence of disease recurrence for 5 years since the initiation of that therapy.
* Prior allogeneic stem cell or solid organ transplantation.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to Approximately 3.5 Years
Secondary outcomes:
measure: Progression-Free survival (PFS)
timeFrame: Up to Approximately 3.5 Years
measure: Best Overall Response (BOR) per Investigator
timeFrame: Up to Approximately 3.5 Years
measure: Duration of Response (DOR) per Investigator
timeFrame: Up to Approximately 3.5 Years
measure: Percentage of Participants with Adverse Events (AE)s
timeFrame: Up to Approximately 3.5 Years
measure: Percentage of Participants with Serious Adverse Events (SAE)s
timeFrame: Up to Approximately 3.5 Years
measure: Percentage of Participants with Treatment Emergent Adverse Events (TEAE)s
timeFrame: Up to Approximately 3.5 Years
measure: Percentage of Participants with Clinically Significant Vital Sign Measurements as Assessed by the Investigator
timeFrame: Up to Approximately 3.5 Years
measure: Percentage of Participants with Clinically Significant Laboratory Values
timeFrame: Up to Approximately 3.5 Years
measure: Percentage of Participants with Immune-Related Reactions as AEs of Special Interest
timeFrame: Up to Approximately 3.5 Years
measure: Maximum Observed Serum Concentration (Cmax) of Livmoniplimab
timeFrame: Up to Approximately 3.5 Years
measure: Cmax of Budigalimab
timeFrame: Up to Approximately 3.5 Years
measure: Time to Reach Cmax (Tmax) of Livmoniplimab
timeFrame: Up to Approximately 3.5 Years
measure: Tmax of Budigalimab
timeFrame: Up to Approximately 3.5 Years
measure: Area Under the Serum Concentration Versus Time Curve (AUC) of Livmoniplimab
timeFrame: Up to Approximately 3.5 Years
measure: AUC of Budigalimab
timeFrame: Up to Approximately 3.5 Years
measure: Clearance (CL) of Livmoniplimab
timeFrame: Up to Approximately 3.5 Years
measure: CL of Budigalimab
timeFrame: Up to Approximately 3.5 Years
measure: Volume of Distribution (Vd) of Livmoniplimab
timeFrame: Up to Approximately 3.5 Years
measure: Vd of Budigalimab
timeFrame: Up to Approximately 3.5 Years
measure: Incidence of Anti-Drug Antibodies (ADAs) of Livmoniplimab
timeFrame: Up to Approximately 3.5 Years
measure: ADAs of Budigalimab
timeFrame: Up to Approximately 3.5 Years
measure: Incidences of Neutralizing Anti-Drug Antibodies (nADAs) of Livmoniplimab
timeFrame: Up to Approximately 3.5 Years
measure: Incidences of nADAs of Budigalimab
timeFrame: Up to Approximately 3.5 Years
Other outcomes:
Locations:
city: Springdale
country: United States
facility: Highlands Oncology Group - Springdale /ID# 270290
state: Arkansas
city: San Francisco
country: United States
facility: University of California San Francisco - Mission Bay /ID# 270289
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine /ID# 270449
state: Connecticut
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants /ID# 271347
state: Delaware
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists - North /ID# 271215
state: Florida
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai /ID# 270272
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center /ID# 271010
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University /ID# 271349
state: Ohio
city: Nashville
country: United States
facility: SCRI Oncology Partners /ID# 270439
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Central /ID# 271284
state: Texas
city: Marseille
country: France
facility: Institut Paoli-Calmettes /ID# 270580
state: Bouches-du-Rhone
city: Suresnes CEDEX
country: France
facility: Hôpital Foch /ID# 270573
state: Hauts-de-Seine
city: Villejuif
country: France
facility: Institut Gustave Roussy /ID# 270575
state: Ile-de-France
city: Haifa
country: Israel
facility: Rambam Health Care Campus /ID# 270105
state: H_efa
city: Kfar Saba
country: Israel
facility: Meir Medical Center /ID# 270108
state: HaMerkaz
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 270096
state: Tel-Aviv
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center /ID# 270106
state: Tel-Aviv
city: Petah Tikva
country: Israel
facility: Rabin Medical Center /ID# 270107
city: Hirosaki
country: Japan
facility: Hirosaki University Hospital /ID# 270531
state: Aomori
city: Fukushima-shi
country: Japan
facility: Fukushima Medical University Hospital /ID# 270752
state: Fukushima
city: Tsukuba-shi
country: Japan
facility: University of Tsukuba Hospital /ID# 270354
state: Ibaraki
city: Kanazawa City
country: Japan
facility: Kanazawa University Hospital /ID# 270473
state: Ishikawa
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center /ID# 270453
state: Gyeonggido
city: Hwasun-gun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital /ID# 271299
state: Jeonranamdo
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital /ID# 270317
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 270898
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center /ID# 270318
state: Seoul Teugbyeolsi
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Bada /ID# 270046
state: Mazowieckie
city: Skorzewo
country: Poland
facility: Aidport Sp. z o.o. /ID# 270049
state: Wielkopolskie
city: Barcelona
country: Spain
facility: Parc de Salut Mar - Hospital del Mar /ID# 270173
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 269783
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona /ID# 269789
city: Madrid
country: Spain
facility: Hospital MD Anderson Cancer Center Madrid /ID# 269780
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos /ID# 269786
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio /ID# 269782
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: