INCA33890 / Incyte, Merus - LARVOL DELTA

Baseline biomarker analysis and clinical outcomes of the PD-1/TGFβR2 bispecific antibody INCA33890 in patients with non-MSI-H metastatic colorectal cancer (mCRC). (ASCO-GI 2026) - P1 | "Funded by Incyte Corporation Clinical Trial Registration Number: NCT05836324 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Biomarker • Clinical • Clinical data • IO biomarker • Metastases • MSI-H • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • MSI • PD-1 • TGFB1 • TGFBR2

INCB161734-101: A Study to Evaluate INCB161734 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation (clinicaltrials.gov) - P1 | N=710 | Recruiting | Sponsor: Incyte Corporation | N=466 ➔ 710

Enrollment change • Solid Tumor • KRAS

Incyte plans to initiate a registrational program for INCA33890 in MSS colorectal cancer in 2026. (Businesswire)

New trial • Colorectal Cancer

A phase I study of INCA33890, a PD-1/TGFβR2 bispecific antibody, for advanced solid tumours (ESMO 2025) - P1 | "Conclusions INCA33890 was generally well tolerated at doses ≤900 mg Q2W. Promising efficacy was seen in a variety of tumour types, including in pts with MSS-CRC with active liver mets."

Metastases • P1 data • Colorectal Cancer • Esophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-1 • TGFB1 • TGFBR2

Incyte Announces Phase 1 Results for its TGFβR2×PD-1 Bispecific Antibody in Advanced Colorectal Cancer… (Businesswire) - "Within this cohort, 16 patients treated with INCA33890 responded (14 confirmed), with 15.2% achieving an objective response rate (ORR) and a median duration of therapy of 7.3 months. The ORR among metastatic MSS colorectal cancer patients treated with INCA33890 was similar across RDE. Deep tumor responses were observed among patients with liver metastasis (n=9) – 12.0% achieved an ORR with a disease control rate (DCR) of 20.0%. Additionally, seven patients with no liver metastases treated with INCA33890 responded, achieving an ORR of 23.3% and DCR of 50.0%."

P1 data • Colorectal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma • Squamous Cell Carcinoma of Head and Neck

Data from Incyte’s TGFβR2×PD-1 Bispecific Antibody and KRAS G12D Inhibitor to be Presented at the European Society of Medical Oncology (ESMO) Congress 2025 (Businesswire) - "...Results from Phase 1 proof-of-concept studies of INCA33890, a promising TGFβR2×PD-1-directed bispecific antibody, and INCB161734, a novel, selective and orally bioavailable KRAS G12D inhibitor, will be highlighted as oral presentations..."

P1 data • Solid Tumor

Incyte To Present Initial Data for its TGFβR2×PD-1-directed Bispecific Antibody (INCA33890) and its Selective Inhibitor of G12D-mutated KRAS (INCB161734) at the European Society of Medical Oncology (ESMO) Congress 2025 (Incyte Press Release) - "Details on the abstracts accepted for oral presentation at ESMO include: (i) INCB161734 (KRAS G12D)​: Preliminary Phase 1 Results Of INCB161734, A Novel Oral KRAS G12D Inhibitor, In Patients With Advanced Or Metastatic Solid Tumors​ (...Abstract #916O); (ii) INCA33890 (PD-1/TGFβR2): A Phase 1 Study Of INCA33890, A PD-1/Tgfβr2 Bispecific Antibody, For Advanced Solid Tumours​ (...Abstract #1522); (iii) INCAGN2385 (LAG-3)​: Retifanlimab (Anti–PD-1 Mab) Alone Or In Combination With Anti-LAG3 ± Anti-TIM3 Mabs In Previously Untreated, Recurrent And/Or Metastatic (R/M) PD-L1+ HNSCC: A Double-Blind Randomised Controlled Phase 2 Trial (...Abstract #1325)."

Clinical data • Squamous Cell Carcinoma of Head and Neck

A Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=408 | Recruiting | Sponsor: Incyte Corporation | N=245 ➔ 408

Enrollment change • Breast Cancer • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Germ Cell Tumors • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • BRAF • ER • HER-2 • PGR • ROS1

PD-1xTGFβR2 bispecific Biclonics® antibody INCA33890 augments human T-cell effector functions in vitro and ex vivo (AACR 2025) - "In this study, various in vitro and ex vivo cell-based systems were used to evaluate changes in T-cell effector function induced by INCA33890 compared with the anti-PD-1 antibodies, nivolumab or pembrolizumab. INCA33890 increased the percentage of IFNγ-producing T cells compared with pembrolizumab over 72 hours. In summary, our data suggest that co-inhibition of both PD-1 and TGFβR2 by INCA33890 may provide greater therapeutic benefits than an anti-PD-1 antibody alone."

IO biomarker • Preclinical • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • GZMB • IFNG • IL2RA • TGFB1 • TGFBR2

INCA33890, a bispecific antibody targeting PD-1 and TGFβR2, shows enhanced immune responses in models of ovarian cancer (AACR 2025) - P1 | "INCA33890 treatment resulted in significantly higher levels of secreted interferon (IFN)-γ compared with control antibodies targeting only PD-1 (pembrolizumab) or TGFβR2 (TGF-1). Altogether, we show that INCA33890 presents a promising immunotherapy option for patients with advanced ovarian cancer by targeting 2 prominent immunosuppressive pathways, leading to a coordinated immune response. Clinical assessment of INCA33890 for various advanced malignancies, including ovarian cancer, is ongoing (NCT05836324)."

IO biomarker • Oncology • Ovarian Cancer • Solid Tumor • CD69 • CD8 • IFNG • IL2RA • PD-L1 • SELL • TGFB1 • TGFBR2 • TNFRSF9

INCA33890 increases CD8+ T-cell effector function compared with pembrolizumab as assessed by single-cell RNA sequencing in human PD-1xTGFβR2 knock-in mouse model (AACR 2025) - "scTCRseq demonstrated a marked increase in the clonality of intratumoral T cells, further underscoring the impactful immune modulation induced by INCA033890. In summary, bispecific Biclonics® targeting of TGFβR2 and PD-1 with INCA33890 promotes the expansion and activation of effector CD8+ T-cell populations within the tumor microenvironment, driving enhanced antitumor activity in vivo."

IO biomarker • Preclinical • Colorectal Cancer • Oncology • Solid Tumor • CD4 • CD8 • TGFB1 • TGFBR2

Incyte Reports 2025 First Quarter Financial Results and Provides Updates on Key Clinical Programs (Businesswire) - "The Phase 3 study evaluating tafasitamab as first-line treatment for DLBCL is ongoing. The Phase 3 data are anticipated in the second half of 2025. The Phase 1 studies evaluating KRASG12D and TGFßR2×PD-1 in solid tumors are ongoing and enrolling patients. Initial proof of concept data for both studies are anticipated in the second half of 2025."

P1 data • P3 data • Diffuse Large B Cell Lymphoma • Solid Tumor

Incyte to Highlight Early-Stage Oncology Data at American Association for Cancer Research Annual Meeting 2025 (Businesswire) - "Incyte...announced that the Company will present new early-stage data from its oncology portfolio at the American Association of Cancer Research (AACR) Annual Meeting 2025 in Chicago, IL, from April 25–30."

Clinical data • Preclinical • Myelofibrosis • Myeloproliferative Neoplasm • Ovarian Cancer

Incyte Reports 2024 Fourth Quarter and Year-End Financial Results, Provides 2025 Financial Guidance and Highlights 2025 R&D Milestones (Businesswire) - "Other Hematology/Oncology – key highlights: Incyte plans to initiate Phase 3 studies for its potentially first-in-class CDK2 inhibitor (INCB123667), in ovarian cancer in 2025 and is also evaluating INCB123667 in combination with other treatments. The Phase 3 study evaluating tafasitamab in first-line DLBCL is ongoing. The Phase 3 data are anticipated in the first half of 2025. The Phase 1 studies evaluating KRASG12D and TGFßR2×PD-1 in solid tumors are ongoing and enrolling patients. Initial proof of concept data for both studies are anticipated in 2025."

New P3 trial • P1 data • P3 data • Diffuse Large B Cell Lymphoma • Ovarian Cancer • Solid Tumor

A Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=245 | Recruiting | Sponsor: Incyte Corporation | N=165 ➔ 245

Enrollment change • Metastases • Breast Cancer • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Germ Cell Tumors • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • BRAF • ER • HER-2 • PGR • ROS1

Incyte Reports 2023 Third Quarter Financial Results and Provides Updates on Key Clinical Programs (Businesswire) - "Oral small molecule PD-L1 program: Combination studies evaluating INCB99280 in combination with axitinib (VEGF) and in combination with ipilimumab (CTLA-4) are enrolling. Two Phase 2 monotherapy studies evaluating INCB99280 in patients with select solid tumors who are checkpoint inhibitor naive and in metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC, are enrolling....INCA33890 (TGFβR2xPD-1): A Phase 1 study evaluating INCA33890 in patients with select advanced solid tumors has been initiated."

Trial status • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

A Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=165 | Recruiting | Sponsor: Incyte Corporation | Not yet recruiting ➔ Recruiting | N=100 ➔ 165 | Trial completion date: May 2026 ➔ Dec 2026 | Trial primary completion date: May 2026 ➔ Dec 2026

Enrollment change • Enrollment open • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Germ Cell Tumors • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • BRAF • ER • HER-2 • PGR • ROS1

Merus Announces Financial Results for the Second Quarter 2023 and Provides Business Update (GlobeNewswire) - "Incyte announced, in 2023, that INCA33890, a novel TGFBr2xPD1 bispecific antibody developed through the collaboration is currently being evaluated in clinical studies. In July 2023, Merus achieved a milestone and expects a payment of $2.5 million related to the advancement of this program in the third quarter of 2023."

Financing • Licensing / partnership • Oncology • Solid Tumor

INCA33890, a novel PD-1×TGFꞵR2 bispecific antibody conditionally antagonizes TGFꞵ signaling in primary immune cells co-expressing PD-1 (AACR 2023) - "Additionally, in two independent PD-1 reporter assays, INCA33890 inhibited SHP recruitment and enhanced NFAT activation with a potency within an order of magnitude to that of pembrolizumab. Collectively, these results provide compelling data for an effective and specific approach to simultaneously antagonizing TGFβ and PD-1 signaling in tumors. Clinical development of INCA33890 in checkpoint inhibitor-resistant and other cancers has been initiated."

Immune cell • IO biomarker • Oncology • Solid Tumor • CD34 • IFNG • PD-1 • TGFBR2

Incyte Reports 2023 First Quarter Financial Results and Provides Updates on Key Clinical Programs (Businesswire) - "At AACR, Incyte presented data demonstrating INCB123667 exhibited significant single-agent activity in vivo in CCNE1high breast cancer xenograft and patient-derived xenograft models....Preclinical in vivo data presented at AACR show that INCA33890 has a greater anti-tumor effect than either individual benchmark antibodies or a simple combination of these."

Preclinical • Breast Cancer • Oncology • Solid Tumor

A Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=100 | Not yet recruiting | Sponsor: Incyte Corporation

Metastases • New P1 trial • Breast Cancer • Colorectal Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Germ Cell Tumors • Head and Neck Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • BRAF • ER • HER-2 • PGR • ROS1