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

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

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…

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=337 | Recruiting | Sponsor: AbbVie | Trial completion date: Feb 2026 ➔ Jun 2027

Combination therapy • Metastases • Trial 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

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 | Not yet recruiting | Sponsor: AbbVie

Adverse events • Combination therapy • Metastases • New P2/3 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Livmoniplimab with or without budigalimab in patients with advanced solid tumors: Results from the combination therapy in the urothelial carcinoma dose expansion cohort. (ASCO-GU 2024) - P1 | "Clinical Trial Registration Number: NCT03821935 Sponsored by AbbVie Background: Checkpoint inhibitors (CPIs) are approved for treating advanced urothelial carcinoma (UC). 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 • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • CD4 • TGFB1

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 | Recruiting | Sponsor: AbbVie | Not yet recruiting ➔ Recruiting | Phase classification: P2 ➔ P2/3

Adverse events • Combination therapy • Enrollment open • Metastases • Phase classification • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

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=337 | Recruiting | Sponsor: AbbVie | Trial completion date: Apr 2024 ➔ Feb 2026 | Trial primary completion date: Apr 2024 ➔ Feb 2026

Combination therapy • Metastases • Trial completion date • 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

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 | N=660 | Not yet recruiting | Sponsor: AbbVie

Adverse events • Combination therapy • Metastases • New P2 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • 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=120 | 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 With Livmoniplimab in Combination With IV Infused Budigalimab in Adult Participants With Hepatocellular Carcinoma (HCC) (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: AbbVie

Adverse events • Checkpoint inhibition • Combination therapy • Metastases • New P2 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Immune Modulation • Oncology • Solid Tumor

Study to Determine the Safety, Tolerability, Pharmacokinetics and Recommended Phase 2 Dose (RP2D) of ABBV-151 as a Single Agent and in Combination With ABBV-181 in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=260 | Recruiting | Sponsor: AbbVie | Trial completion date: Oct 2023 ➔ Apr 2024 | Trial primary completion date: Apr 2023 ➔ Apr 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • 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

Budigalimab Plus ABBV-151 Demonstrates Variable Activity Across Locally Advanced or Metastatic Solid Tumors (OncLive) - P1 | N=260 | NCT03821935 | Sponsor: AbbVie | "The addition of budigalimab to ABBV-151 was well tolerated and significantly enhanced responses in patients with locally advanced or metastatic solid tumors, according to findings from a phase 1 trial (NCT03821935) presented at the 2022 SITC Annual Meeting. The objective response rate (ORR) was 10% (95% CI, 5.7%-15.5%) in the overall population (n = 163). The ORR was 0% with ABBV-151 in dose-escalation and 12% with the combination. The ORR was 16% (95% CI, 6.2%-32.0%) in the patients with urothelial cancer that was relapsed/refractory to PD-1 inhibition. The ORRs were 33% (95% CI, 9.9%-65.1%), 0%, and 8% (95% CI, 1.0%-26.0%) in the patients with PD-1–naïve hepatocellular carcinoma (HCC), pancreatic cancer, and microsatellite stable colorectal cancer (MSS-CRC), respectively."

P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Safety, efficacy, and pharmacokinetic results from a phase I first-in-human study of ABBV-151 with or without anti-PD1 mAb (budigalimab) in patients with locally advanced or metastatic solid tumors (SITC 2022) - P1 | "Conclusions ABBV-151 ± budigalimab showed a manageable safety profile in patients with advanced solid tumors. Preliminary efficacy results demonstrate durable antitumor activity with ABBV-151 + budigalimab, including in anti-PD-1 relapsed/refractory UC and in anti-PD-1 naïve HCC."

Clinical • P1 data • PK/PD data • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Urothelial Cancer • TGFB1

Study to Determine the Safety, Tolerability, Pharmacokinetics and Recommended Phase 2 Dose (RP2D) of ABBV-151 as a Single Agent and in Combination With ABBV-181 in Participants With Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=260 | Recruiting | Sponsor: AbbVie | Trial primary completion date: Oct 2023 ➔ Apr 2023

Combination therapy • Trial primary completion date • Colorectal Adenocarcinoma • 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

"$ABBV says ABBV-151 differentiated from previous TGFβ1 failures, as "GARP blocks the inactive form of TGF-beta before it's released"" (@ByMadeleineA)

TGFB1