livmoniplimab (ABBV-151) / AbbVie, argenx - LARVOL DELTA

A phase 2, open-label, randomized study of livmoniplimab in combination with budigalimab versus chemotherapy in patients with metastatic urothelial carcinoma. (ASCO 2025) - P1, P2 | "While immune checkpoint inhibitors (CPI), including programmed cell death protein 1 (PD-1) inhibitors combined with chemotherapy (CTx) or enfortumab vedotin (EV), have been approved for first-line treatment of metastatic (m)UC, many pts have de novo or develop acquired resistance...Pts will be randomized 1:1:1 to 3 arms: 1) livmo dose 1 Q3W + budi Q3W; 2) livmo dose 2 Q3W + budi Q3W; or 3) investigator's choice of CTx (paclitaxel, docetaxel, or gemcitabine). Pts will be stratified by ECOG PS (0 vs 1) and first-line therapy (pembrolizumab + EV vs CTx)...For all pts, treatment is discontinued at disease progression or if other protocol-defined discontinuation criteria are met. In total, approximately 150 pts (50 pts/arm) are planned for enrollment globally."

Clinical • Combination therapy • Metastases • P2 data • Oncology • Solid Tumor • Urothelial Cancer • TGFB1

AbbVie Features New Data Across Difficult-to-Treat Solid Tumors and Blood Cancers at ASCO 2025, Highlighting Breadth and Depth of its Oncology Portfolio (PRNewswire) - "AbbVie...announced that key data from its broad oncology portfolio will be showcased across multiple oral presentations and posters at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting (May 30 - June 3, 2025). These new data highlight significant progress in AbbVie's robust oncology pipeline, across a range of difficult-to-treat solid tumors and blood cancers."

Clinical data • B Cell Non-Hodgkin Lymphoma • Castration-Resistant Prostate Cancer • Prostate Cancer • Urothelial Cancer

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 (clinicaltrials.gov) - P1 | N=364 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Enrollment closed • Colorectal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

LIVIGNO-2: A Study to Assess the Dose, Adverse Events, and Change in Disease Activity of Livmoniplimab as an Intravenous (IV) Solution in Combination With Budigalimab as an IV Solution in Adult Participants With Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P2/3 | N=660 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Adverse events • Enrollment closed • Hepatocellular Cancer • Oncology • Solid Tumor

Livmoniplimab and budigalimab for patients with metastatic ovarian granulosa cell tumors: results from Phase 1 study (JSMO 2025) - No abstract available

Clinical • Metastases • P1 data • Oncology • Ovarian Cancer

Livmoniplimab and budigalimab for advanced solid tumors: Results from dose expansion cohort for urothelial carcinoma (JSMO 2025) - No abstract available

Metastases • Oncology • Solid Tumor • Urothelial Cancer

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) (clinicaltrials.gov) - P2 | N=150 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Adverse events • Enrollment open • Metastases • Oncology • Solid Tumor • Urothelial Cancer

Anti-tumor T cell response and immunoselection under combined GARP:TGF-_1/PD-1 blockade (ESMO-IO 2024) - "Background Livmoniplimab (livmo) is a monoclonal anti-GARP:TGF-β1 antibody currently tested in combination with budigalimab (budi) in phase 1 and 2 trials for several cancer indications. Increase in the frequency of the two anti-BLZF1mut T cell clones after one cycle of treatment correlated with a reduction in the ratio of mutated BLZF1 to mutated TP53 alleles in the metastasis, suggesting increased cytotoxic activity and immunoselection by the anti-BLZF1 oligoclonal T cell response in the course of treatment.Conclusions Our results indicate that tumor-infiltrating CD8 T cells against mutated antigens can be amplified in response to livmo + budi, and exert cytolytic activity and immunoselection on tumor cells expressing the cognate antigens. Given that all patients included were refractory to previous anti-PD(L)1 therapy, our data suggests that the biological anti-tumor activity observed in the biopsy from one patient results at least in part from the activity of livmo."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD8 • TGFB1 • TP53

Livmoniplimab with or without budigalimab in patients with advanced solid tumors: Results from the combination therapy in the urothelial carcinoma dose expansion cohort (AIOM 2024) - P1 | "Background : Checkpoint inhibitors(CPIs) are approved for advanced(adv) urothelial carcinoma(UC). Livmo+budi had manageable safety and promising efficacy in pts with adv UC progressed on platinum-based therapy and CPI. UC cohort ORR(pts postprogression with platinum+CPI therapy) are comparable with CPI-naive pts ORR with pembrolizumab(KN-045) and nivolumab(CM-275) monotherapy. A subpopulation of pts in UC cohort had durable response to livmo+budi."

Clinical • Combination therapy • Metastases • Anemia • Dermatology • Hematological Disorders • Oncology • Pruritus • Solid Tumor • Urothelial Cancer • CD4 • TGFB1

Livmoniplimab and budigalimab combination therapy in treating patients with metastatic ovarian granulosa cell tumors: results from dose escalation in a first-in-human study (AIOM 2024) - P1 | "Several agents with different targets, such as pembrolizumab, nirogacestat, orteronel and STM 434, are being evaluated but to date without clinical benefit...She had received 7 prior lines of therapy including doxorubicin, bevacizumab, anastrozole, tamoxifen and carboplatin+paclitaxel... Livmo+budi had promising antitumor efficacy and tolerablesafety profile in pts with metastatic OGC. All enrolled pts showed tumor shrinkage and 1 pt had durable and near-complete response. Since singleagent pembrolizumab exhibited an ORR of 0%(How et al."

Clinical • Combination therapy • Metastases • P1 data • Anemia • Fatigue • Hematological Disorders • Hepatology • Oncology • Ovarian Cancer • Solid Tumor • FOXL2 • TGFB1

Livmoniplamab dose selection for dose optimization in patients with solid tumors to address project optimus: application of translational approach and pharmacokinetic-pharmacodynamic modeling (SITC 2024) - P1 | "It is being investigated in combination with budigalimab (anti-PD-1) in patients with solid tumors. Conclusions PK/PD modeling leveraging clinical and pre-clinical data identified 400 mg Q3W and 1200 mg Q3W as minimal doses required to achieve maximal target engagement and TGF-β1 inhibition in the TME. Livmoniplimab 400 mg Q3W and 1200 mg Q3W are being explored in multiple Phase 2 studies."

Clinical • PK/PD data • Oncology • Solid Tumor • TGFB1

First-in-human phase 1 dose-escalation results with livmoniplimab, an antibody targeting the GARP:TGF-ß1 complex, as monotherapy and in combination with the anti-PD-1 antibody budigalimab in patients with advanced solid tumors. (PubMed, Front Oncol) - P1 | "Livmoniplimab was well-tolerated as monotherapy and in combination with budigalimab in the dose-escalation phase. Encouraging preliminary efficacy was demonstrated in the combination dose escalation in heavily pretreated patients, supporting further development of this novel drug combination in patients with advanced solid tumors."

Combination therapy • IO biomarker • Journal • Metastases • Monotherapy • P1 data • Dermatology • Fatigue • Hematological Disorders • Oncology • Pruritus • Solid Tumor

LIVIGNO-1: Study to Evaluate Adverse Events, and Change in Disease Activity, When Intravenously (IV) Infused With Livmoniplimab in Combination With IV Infused Budigalimab in Adult Participants With Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P2 | N=130 | Active, not recruiting | Sponsor: AbbVie | Recruiting ➔ Active, not recruiting

Adverse events • Checkpoint inhibition • Combination therapy • Enrollment closed • Metastases • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

A Study to Assess the Adverse Events and How Intravenously Infused Livmoniplimab in Combination With Budigalimab Moves Through the Bodies of Adult Chinese Participants With Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Adverse events • Checkpoint inhibition • Combination therapy • Enrollment open • Metastases • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

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) (clinicaltrials.gov) - P2 | N=150 | Not yet recruiting | Sponsor: AbbVie

New P2 trial • Oncology • Solid Tumor • Urothelial Cancer

A phase II/III study to evaluate the optimal dose, safety, and efficacy of livmoniplimab (Livmo) in combination with budigalimab (Budi) plus chemotherapy (CT) vs pembrolizumab (Pembro) plus CT in untreated metastatic non-small cell lung cancer (mNSCLC) (ESMO 2024) - P2/3 | "Enrollment is ongoing in ∼200 sites globally. Table: 1393TiP RP3D, recommended phase III dose; BOR, best overall response; C/PR, complete/partial response; Inv, investigator; PFS, progression-free survival; DOR, duration of response; OS, overall survival; PRO, patient reported outcome; BICR, blinded central review"

Clinical • Combination therapy • IO biomarker • Metastases • P2/3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-1 • PD-L1 • TGFB1

A Study to Assess the Adverse Events and How Intravenously Infused Livmoniplimab in Combination With Budigalimab Moves Through the Bodies of Adult Chinese Participants With Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P1 | N=20 | Not yet recruiting | Sponsor: AbbVie

Adverse events • Checkpoint inhibition • Combination therapy • Metastases • New P1 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Phase 2/3 study of livmoniplimab in combination with budigalimab in patients with locally advanced or metastatic hepatocellular carcinoma. (ASCO 2024) - P2/3 | "Stage 1 is a phase 2 dose-optimization lead-in, during which ~80 patients will be enrolled and randomized 1:1:2 to receive 1 of 2 doses of livmoniplimab in combination with budigalimab Q3W, or investigator's choice of either atezolizumab + bevacizumab Q3W or single-dose tremelimumab + durvalumab Q4W per STRIDE regimen. Secondary objectives include assessment of safety, tolerability, immunogenicity, and PK, efficacy measured by median progression-free survival, ORR, and duration of response as well as the impact on patient-reported outcomes. Enrollment is planned in Europe, Asia, and USA, and is open as of Dec 2023."

Clinical • Combination therapy • Metastases • P2/3 data • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • TGFB1

Phase 2 study of livmoniplimab in combination with budigalimab in patients with hepatocellular carcinoma. (ASCO 2024) - P1 | "Pts (n=120) will be randomized 1:1:1 to receive 400mg sorafenib BID/8-12mg lenvatinib QD orally (control; investigator choice), low- or high-dose IV livmo (selected based on mode of action, clinical efficacy and safety, and clinical PK/PD modeling) + IV budi Q3W in 21-day cycles. The RP3D for livmo will be selected based on all available preclinical and clinical data. Enrollment began in July 2023 and up to 60 sites in ~7 countries will be included."

Clinical • Combination therapy • IO biomarker • P2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • TGFB1

Livmoniplimab with or without budigalimab in patients with advanced solid tumors: Results from the combination therapy in the urothelial carcinoma dose expansion cohort. (ASCO 2024) - P1 | "Research Funding: AbbVie. Livmo + budi had manageable safety and promising efficacy in pts with advanced UC that progressed on platinum-based therapy and a CPI. ORR in the UC cohort (pts postprogression with platinum + CPI therapy) are comparable with ORR in CPI-naive pts with pembrolizumab (KEYNOTE-045) and nivolumab (CheckMate 275) monotherapy. A subpopulation of pts in the UC cohort had a durable response to livmo + budi."

Clinical • Combination therapy • Metastases • Anemia • Dermatology • Hematological Disorders • Oncology • Pruritus • Solid Tumor • Urothelial Cancer • CD4 • TGFB1

Targeting GARP–TGF-β1 with livmoniplimab plus anti–PD-1 budigalimab to remodel the immunosuppressive tumor microenvironment. (ASCO 2024) - P1, P2 | "These data demonstrate that livmo induces decrease in tumor cell viability, increased antitumor immune cell activation, and remodeling of the immune-suppressive TME, which is further enhanced in combination with budi. These results support the hypothesis that pts would benefit from therapeutic intervention with livmo + budi. 1."

Biomarker • Tumor microenvironment • Bladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • GZMB • IFNG • TGFB1

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 (clinicaltrials.gov) - P1 | N=362 | Recruiting | Sponsor: AbbVie | Trial primary completion date: Feb 2026 ➔ Jun 2027

Combination therapy • Metastases • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Livmoniplimab and budigalimab combination therapy in treating patients with metastatic ovarian granulosa cell tumors: Results from dose escalation in a first-in-human study (AACR 2024) - P1 | "Several agents with different targets, such as pembrolizumab, nirogacestat, orteronel, and STM 434, are being evaluated but to date have not shown clinical benefit...She had received 7 prior lines of therapy including doxorubicin, bevacizumab, anastrozole, tamoxifen, and carboplatin + paclitaxel... Livmo + budi had promising antitumor efficacy and a tolerable safety profile in pts with metastatic OGC, a rare TGF-β signaling-dependent tumor. All enrolled pts with OGC showed tumor shrinkage and 1 pt had durable and near-complete response. Since single-agent pembrolizumab exhibited an ORR of 0% in pts with OGC (How et al."

Clinical • Combination therapy • IO biomarker • Metastases • P1 data • Oncology • Ovarian Cancer • FOXL2 • TGFB1

LIVIGNO-4: Study to Evaluate Adverse Events, Optimal Dose, and Change in Disease Activity, With Livmoniplimab in Combination With Budigalimab Plus Chemotherapy Versus IV Infused Pembrolizumab Plus Chemotherapy in Adult Participants With Untreated Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2/3 | N=840 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting

Adverse events • Combination therapy • Enrollment open • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

#GU24 #bladdercancer highlights - AMBASSADOR @apolo_andrea (adjuvant pembrolizumab for high-risk muscle-invasive #urothelialcarcinoma following surgery), EV302 @MichvdHeijden (first-line EV+pembrolizumab for metastatic UC), Dato-DXd as salvage therapy, Pembro + cabozantinib @rohitjainMD as first-line therapy for cis/plat-ineligible/refusing metastatic UC, APL-1202 (oral MetAP2 inhibitor…