INCA33890 / Incyte, Genmab - LARVOL DELTA

INCA33890, a TGFβR2xPD-1 Bispecific Antibody, With Standard of Care (SoC) Anticancer Therapies for Microsatellite Stable Colorectal Cancer (MSS CRC) (ESMO 2026) - No abstract available

Bispecific • Colorectal Cancer • Oncology • Solid Tumor • TGFB1 • TGFBR2

NEXERA-204: A Study to Evaluate INCA33890 in the Treatment of Circulating Tumor DNA-Positive Stage II/III Microsatellite Stable Colorectal Cancer After Curative Resection and Chemotherapy (clinicaltrials.gov) - P2 | N=40 | Not yet recruiting | Sponsor: Incyte Corporation

Circulating tumor DNA • New P2 trial • Colorectal Cancer • Oncology • Solid Tumor

Incyte Data to Be Highlighted in Four Rapid Oral Presentations at the European Society for Medical Oncology (ESMO) Congress 2026 Support Efforts to Improve Outcomes in Difficult-to-Treat Cancers (Incyte Press Release) - "Rapid oral presentations will highlight new Phase 1 data across Incyte’s solid tumor portfolio; Both INCB161734, an investigational, potent, selective and orally bioavailable KRAS G12D inhibitor, and INCA33890, a TGFβR2×PD-1 bispecific antibody, are being evaluated in ongoing Phase 3 programs as first-line treatments for patients with advanced pancreatic ductal adenocarcinoma (PDAC) and microsatellite stable (MSS) colorectal cancer, respectively."

First-in-human • P1 data • P3 data • Anal Squamous Cell Carcinoma • Colorectal Cancer • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Pancreatic Ductal Adenocarcinoma • Peritoneal Cancer

INCA 33890-101: A Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=570 | Recruiting | Sponsor: Incyte Corporation | N=408 ➔ 570 | Trial completion date: Jan 2027 ➔ May 2029 | Trial primary completion date: Jan 2027 ➔ May 2029

Enrollment change • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

INCA033890-303: A randomized, double-blind, phase 3 study of FOLFOX and bevacizumab with or without INCA33890 in the first-line treatment of metastatic microsatellite-stable colorectal cancer. (ASCO 2026) - P1, P3 | "Additional secondary endpoints are ORR, safety and tolerability, duration of response, and patient-reported outcomes. Trial enrollment is ongoing."

Clinical • IO biomarker • Metastases • P3 data • Colorectal Cancer • Immunology • Microsatellite Instability • Oncology • Solid Tumor • BRAF • MSI • PD-L1 • TGFBR2

INCA033890-303: A Randomized, Double-Blind, Phase 3 Study of Standard-of-Care Chemotherapy and Bevacizumab With or Without INCA33890 in the First-Line Treatment of Metastatic Microsatellite Stable Colorectal Cancer (clinicaltrialsregister.eu) - P2/3 | N=106 | Not yet recruiting | Sponsor: Incyte Corp.

New P2/3 trial • Colorectal Cancer • Oncology • Solid Tumor

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."

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

Key Business Updates (Incyte Press Release) - "The Company initiated a Phase 3 study (DAWN-303) evaluating INCB161734 as a first-line treatment in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) in combination with standard-of-care chemotherapy (mFOLFIRINOX or GEMNabP) versus chemotherapy alone in the first quarter of 2026; Additional data from the ongoing Phase 1 trial evaluating INCB161734 in combination with standard-of-care chemotherapy as a first-line treatment in patients with metastatic PDAC are anticipated in the second half of 2026...The Phase 3 study evaluating INCA33890 in....patients with microsatellite stable colorectal cancer (MSS CRC) is ongoing; Additional data from the ongoing Phase 1 study evaluating INCA33890...in patients with solid tumors is expected in the second half of 2026."

P1 data • Trial status • Colorectal Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

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)."

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

Pharmacodynamic biomarkers of TGFβR2xPD-1 bispecific antibody INCA33890 in patients with MSS metastatic colorectal cancer (mCRC) (AACR 2026) - P1 | "At the recommended doses for expansion, INCA33890 binding was specific for PD-1+ T cells, as evidenced by low anti-idiotype binding on naïve T cells, which do not express PD-1. Decreases in pSMAD and T-cell TGFβR2 response signature in intratumoral T cells demonstrated the inhibition of TGFβR2 by INCA33890."

Biomarker • Bispecific • Clinical • IO biomarker • Metastases • PK/PD data • Colorectal Cancer • Oncology • Solid Tumor • CD4 • CD8 • CXCL10 • CXCL9 • FOXP3 • GZMB • IFNG • TGFB1 • TGFBR2

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

Adagene Announces Clinical Collaboration with Incyte to Evaluate Muzastotug (ADG126) in Combination with Incyte’s TGFßR2xPD-1 Bispecific Antibody (INCA33890) in Patients with Microsatellite Stable Colorectal Cancer (MSS CRC) (GlobeNewswire) - "Under terms of the agreement, Incyte will sponsor and conduct the study and Adagene will provide clinical trial supply of muzastotug. The planned dose escalation portion of the study will evaluate safety and tolerability, followed by an efficacy expansion cohort in patients with chemotherapy-refractory MSS CRC patients with and without liver metastases....Phase 1 study of INCA33890 and muzastotug expected to begin in 2026 in 3L MSS CRC patients with and without liver metastases."

Commercial • New P1 trial • Colorectal Cancer

A Study to Evaluate the Efficacy and Safety of Standard-of-Care Chemotherapy and Bevacizumab With or Without INCA33890 in the First-Line Treatment of Metastatic Microsatellite Stable Colorectal Cancer (clinicaltrials.gov) - P3 | N=700 | Recruiting | Sponsor: Incyte Corporation | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor

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 | "INCA33890 demonstrated preliminary efficacy in pts with non-MSI-H mCRC across a variety of subgroups. Higher baseline PD-L1 expression and mRNA expression of inflammatory genes enriched for clinical benefit while overexpression of TGF-β did not seem to enhance efficacy. Updated data will be presented."

Biomarker • Clinical • Clinical data • IO biomarker • Metastases • MSI-H • Tumor mutational burden • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD8 • CXCL10 • CXCL9 • IFNG • KRAS • MSI • PD-1 • PD-L1 • SMAD4 • TGFB1 • TGFBR2 • TMB • TP53

A Study to Evaluate the Efficacy and Safety of Standard-of-Care Chemotherapy and Bevacizumab With or Without INCA33890 in the First-Line Treatment of Metastatic Microsatellite Stable Colorectal Cancer (clinicaltrials.gov) - P3 | N=700 | Not yet recruiting | Sponsor: Incyte Corporation

New P3 trial • Colorectal Cancer • Oncology • Solid Tumor

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

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