CUE-101 / Cue Biopharma, LG Chem - LARVOL DELTA

Personalized and HPV cancer vaccines in head and neck squamous cell carcinoma: from concept to clinical implementation. (PubMed, Transl Oncol) - "Compounds such as TG4050, mRNA-4157, and PGV001 have shown early, hypothesis-generating signals of activity (from small early-phase studies), particularly in the adjuvant setting. HPV-targeted vaccines, including PDS0101, BNT113, and CUE-101, are being explored in HPV-positive HNSCC, mainly in combination with ICIs...The greatest clinical potential of therapeutic vaccination may lie in earlier disease stages, where the tumor burden is lower and immune modulation more feasible. Further clinical and translational research is needed to define the optimal integration of vaccine-based therapies into multimodal treatment paradigms for HNSCC."

IO biomarker • Journal • Review • Head and Neck Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

KEYNOTE-A78: A Phase 1 Study in Patients With HPV16+ Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P1 | N=80 | Completed | Sponsor: Cue Biopharma | Active, not recruiting ➔ Completed

First-in-human • Monotherapy • Trial completion • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDKN2A • CTLA4

CUE-101with Pembrolizumab for LA-HPV+HNSCCs (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: Yale University

New P2 trial • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Cue Biopharma Reports Second Quarter 2025 Financial Results and Recent Business Highlights (GlobeNewswire) - "Poster presentation delivered by Dana-Farber Cancer Institute at the American Society of Gene & Cell Therapy Annual Meeting presented proof-of-concept data on CUE-101 and its potential to control CAR-T cell expansion and persistence in vivo."

Preclinical • Oncology

Cue Biopharma Reports New Complete Response and Confirmed 50% Overall Response Rate in Ongoing Phase 1 Trial of CUE-101 and Pembrolizumab in Recurrent/Metastatic HPV+ Head and Neck Cancer (GlobeNewswire) - P1 | N=85 | KEYNOTE-048 (NCT03978689) | Sponsor: Cue Biopharma | "Key data highlights from the expansion portion of the trial evaluating CUE-101 at the recommended Phase 2 dose (RP2D) of 4mg/kg in combination with pembrolizumab in 1L patients (data cutoff of July 14, 2025) include: ORR of 50% (2 CR and 10 partial responses (PR) in patients with CPS ≥1, compared to an ORR of 19% observed with pembrolizumab alone in the historical third-party KEYNOTE-048 trial); Survival metrics have continued to mature favorably: 12-month overall survival (OS) of 88% compared to 57% with pembrolizumab alone in the historical KEYNOTE-048 trial, representing a reduction in the risk of death (HR 0.23) compared to historical data; mOS of 32 months compared to 12.3 months in the historical KEYNOTE-048 trial; ORR of 50% in patients, including 50% with low PD-L1 expression CPS (1-19)."

P1 data • Head and Neck Cancer • Squamous Cell Carcinoma of Head and Neck

Cue Biopharma Provides Update on Most Advanced Clinical Stage Asset, CUE-101, Presented by Dr. Dimitrios Colevas at the DAVA 4th Hawaii Global Summit on Thoracic Malignancies (GlobeNewswire) - P1 | N=85 | NCT03978689 | Sponsor: Cue Biopharma | "Dr. Dimitrios Colevas presented new data from the company’s maturing Phase 1 trial evaluating CUE-101 in combination with KEYTRUDA (pembrolizumab) for patients with recurrent metastatic HPV+ head and neck squamous cell carcinoma (HNSCC). Data highlights include an overall response rate (ORR) of 50% (with 1 unconfirmed PR) in patients with combined positive score (CPS) >1 and an ORR of 50% observed in patients with low CPS scores (1-19). This compares favorably to the historical ORR of 19% observed with pembrolizumab alone in the third-party KEYNOTE 048 trial. Notably, the 12-month overall survival (OS) of 88% in the Phase 1 trial represents a significant reduction in the risk of death (HR 0.23) compared to historical data from the KEYNOTE 048 study. The Kaplan-Meier (K-M) estimate for median overall survival (mOS) is currently 32 months."

P1 data • Squamous Cell Carcinoma of Head and Neck

Safety of administration of CUE-101, a novel HPV16 E7-pHLA-IL2-Fc fusion protein, before curative-intent treatment in patients with HPV16+ oropharyngeal squamous cell carcinoma. (ASCO 2025) - P1, P2 | "Administration of CUE-101 (4 mg/kg IV) 14 days (Schedule A) and 14 and 7 days (Schedule B) before curative-intent treatment was safe and tolerable. Follow-up in Schedules A and B is ongoing. Schedule C is actively accruing patients."

Clinical • Anemia • Back Pain • Eosinophilia • Fatigue • Hematological Disorders • Musculoskeletal Pain • Oncology • Oropharyngeal Cancer • Pain • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IL2

Characterization of dynamic changes in tumor-infiltrating lymphocytes (TIL) after neoadjuvant administration of CUE-101, an HPV16 E7-HLA-IL2 fusion protein, to patients with HPV+ locally advanced oropharyngeal squamous cell carcinoma (LA-OPSCC). (ASCO 2025) - P2 | "Significant clonal expansion of intra-tumoral CD8 T-cells with signatures associated with tumor reactivity were observed within 2 weeks of CUE-101 administration in HPV16+ LA OPSCC. Studies in blood and of T-cell specificities are ongoing."

Clinical • IO biomarker • Metastases • Tumor-infiltrating lymphocyte • Oncology • Oropharyngeal Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • ENTPD1 • IL2 • PD-1 • PTPRC

Leveraging Immuno-STAT stimulation via TCR and IL-2 signaling to specifically control CAR T cell expansion and persistence in vivo (ASGCT 2025) - P1 | "IL-2 signaling through a CAR-independent circuit uniquely eradicated solid tumor models [1], but the clinical utility of non-specific cytokine CAR-T support (e.g. IL2; aldesleukin) is limited by toxicity...The first clinical-stage Immuno-STAT, CUE-101, selectively activates and expands HPV-specific CD8+ T-cells and is associated with durable anti-tumor responses in HPV+ recurrent/metastatic head and neck cancers, with the objective response rate more than doubled in combination with pembrolizumab vs historic control of pembrolizumab alone (NCT03978689, [3])... We demonstrate that Immuno-STAT treatment together with engineering co-expression of cognate exogenous TCR can specifically control the expansion and persistence of CAR-T cells. Leveraging the clinical experience with CUE-101, we anticipate future evaluation of this approach to determine whether Immuno-STAT-controlled expansion of E.T.CAR-T can enhance and control expansion/persistence of adoptive cellular..."

CAR T-Cell Therapy • IO biomarker • Preclinical • Head and Neck Cancer • Hematological Malignancies • Oncology • Solid Tumor • CD8 • IL2

Cue Biopharma Reports First Quarter 2025 Financial Results and Recent Business Highlights (GlobeNewswire) - "Upcoming Event: Novel Biologics Portfolio Virtual Event planned for May 15, 2025 at 11 AM ET: Cue Biopharma’s virtual event will feature two key opinion leaders (KOLs): Richard DiPaolo, PhD (Saint Louis University) and Andrew Cope, MD, PhD (Centre for Rheumatic Diseases, King's College London). The event will highlight new preclinical data for CUE-401...and include key updates on the CUE-100 series clinical oncology programs."

Clinical • Preclinical • Immunology • Inflammation • Oncology

KEYNOTE-A78: A Phase 1 Study in Patients with HPV16+ Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P1 | N=85 | Active, not recruiting | Sponsor: Cue Biopharma | Trial completion date: May 2025 ➔ Jan 2026 | Trial primary completion date: Nov 2024 ➔ Jan 2026

Monotherapy • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDKN2A • CTLA4

A phase 1 dose-escalation and expansion study of CUE-101 as monotherapy and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck squamous cell cancer (SITC 2024) - P1 | "Ethics Approval This study was approved by Ethics and Institutional Review Boards (IRBs) at all study sites. IRB reference numbers: Advarra Pro00037736 (Moffitt Cancer Center), IRB 52744 (Stanford University School of Medicine), HRPO# 201905108 (Washington University School of Medicine), DF/HCC IRB# 19-374 (Massachusetts General Hospital), WIRB STUDY00008948 (University of Washington, Seattle), IRB 191714 (Vanderbilt University Medical Center Vanderbilt-Ingram Cancer Center), 2019-087 Karmanos Cancer Institute, WIRB 2000026098 (Yale Cancer Center), 2019-0578 (The University of Texas MD Anderson Cancer Center), WIRB 1908869642 (University of Arizona Cancer Center), WIRB IRB00112341(Winship Cancer Institute/Emory University), IRB 20-073 (Memorial Sloan Kettering Cancer Center), IRB00255391 (Johns Hopkins University School of Medicine), IRB(IRBMED) HUM00165746 (University of Michigan Comprehensive Cancer Center), IRB0001113 (US Oncology Inc./Affiliated Oncologists,..."

Clinical • Combination therapy • Metastases • Monotherapy • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IL2

A phase 1 dose-escalation and expansion study of CUE-101 as monotherapy and in combination with pembrolizumab in patients with recurrent/metastatic HPV16+ head and neck squamous cell cancer (SITC 2024) - P1 | "Ethics Approval This study was approved by Ethics and Institutional Review Boards (IRBs) at all study sites. IRB reference numbers: Advarra Pro00037736 (Moffitt Cancer Center), IRB 52744 (Stanford University School of Medicine), HRPO# 201905108 (Washington University School of Medicine), DF/HCC IRB# 19-374 (Massachusetts General Hospital), WIRB STUDY00008948 (University of Washington, Seattle), IRB 191714 (Vanderbilt University Medical Center Vanderbilt-Ingram Cancer Center), 2019-087 Karmanos Cancer Institute, WIRB 2000026098 (Yale Cancer Center), 2019-0578 (The University of Texas MD Anderson Cancer Center), WIRB 1908869642 (University of Arizona Cancer Center), WIRB IRB00112341(Winship Cancer Institute/Emory University), IRB 20-073 (Memorial Sloan Kettering Cancer Center), IRB00255391 (Johns Hopkins University School of Medicine), IRB(IRBMED) HUM00165746 (University of Michigan Comprehensive Cancer Center), IRB0001113 (US Oncology Inc./Affiliated Oncologists,..."

Clinical • Combination therapy • Metastases • Monotherapy • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IL2

Cue Biopharma Presents Positive Updated Data from its Phase 1 Trial of CUE-101…in Head and Neck Cancer…at the SITC 39th Annual Meeting (GlobeNewswire) - P1 | N=85 | NCT03978689 | Sponsor: Cue Biopharma | "Key data highlights from the expansion portion of the trial evaluating CUE-101 at the recommended Phase 2 dose (RP2D) of 4mg/kg in combination with pembrolizumab...include: ORR of 46% and overall disease control rate (DCR) of 75% in patients with combined positive score (CPS) ≥1, compared to an ORR of 19% observed with pembrolizumab alone in the historical third-party KEYNOTE-048 trial. This includes one complete response (CR) and 10 partial responses (PR), in addition to seven durable stable diseases (DSD) of >12 weeks....Key data highlights from the CUE-101 expansion portion of the Phase 1b trial evaluating CUE-101 at the RP2D as monotherapy...include: mOS of 20.8 months, notably longer than the historical mOS of 7.5 and 8.4 months reported in historical third-party 2L R/M HNSCC trials: CheckMate 141 and KEYNOTE-040, respectively."

P1 data • Squamous Cell Carcinoma of Head and Neck

Cue Biopharma Announces Upcoming Scientific Presentations at the Society for Immunotherapy of Cancer’s (SITC) 39th Annual Meeting (GlobeNewswire) - "Cue Biopharma...announced it will deliver an oral and a poster presentation on the company’s Immuno-STAT clinical assets CUE-101 and CUE-102, representative of the CUE-100 series, at the Society for Immunotherapy of Cancer’s 39th Annual Meeting (SITC 2024). The conference will be held in Houston, Texas, on November 6-10, 2024."

P1 data • Squamous Cell Carcinoma of Head and Neck

Cue Biopharma to Present at The Promise of Interleukin-2 Therapy Conference (GlobeNewswire) - "Cue Biopharma, Inc...today announced that members of its management team will deliver two presentations at The Promise of Interleukin-2 Therapy Conference, taking place September 4-7, 2024 in Paris, France....Dr. Levisetti will discuss how the company’s lead oncology programs CUE-101 and CUE-102, representative of the CUE-100 series of Immuno-STAT™ biologics, enable selective targeting of the cytokine IL-2 to tumor specific T cells for enhanced efficacy and safety profiles."

Clinical data • Oncology • Solid Tumor

Cue Biopharma to Host Business Update Call and Webcast (GlobeNewswire) - "Cue Biopharma, Inc...announced today that it will host a conference call and webcast to provide a business update on Monday, August 19, 2024 at 4:30 p.m. EDT. The company will provide a business overview of its recent restructuring and near-term strategic prioritization objectives. The discussion will focus on the...enabling data from its ongoing oncology trials for CUE-101 and CUE-102 to continue to mature. Additional clinical and business updates, as well as market opportunities and anticipated near-term milestones, will also be addressed."

Clinical data • Oncology

A phase 1 dose-escalation and expansion study of CUE-101, given as monotherapy and in combination with pembrolizumab, in patients with recurrent/metastatic HPV16+ head and neck squamous cell cancer (R/M HNSCC). (ASCO 2024) - P1 | "An ORR of 47% and a mPFS of 5.8 months were observed in R/M HNSCC patients treated with CUE-101 4 mg/kg + pembrolizumab as 1L therapy. A median OS of 20.8 was observed in patients treated with CUE-101 monotherapy as post-platinum/CPI therapy. CUE-101 continues to demonstrate safety, tolerability and meaningful clinical benefit in patients with HPV16+ R/M HNSCC."

Clinical • Combination therapy • Metastases • Monotherapy • P1 data • Anemia • Head and Neck Cancer • Hematological Disorders • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • IL2 • PD-L1

Cue Biopharma Presents Updated Data from Phase 1 Trial of CUE-101 in Recurrent/Metastatic HPV+ Head and Neck Cancer at the 2024 ASCO Annual Meeting (GlobeNewswire) - P1b | N=85 | NCT03978689 | Sponsor: Cue Biopharma | "Key data highlights to date from the expansion portion of the trial evaluating CUE-101 at the recommended Phase 2 dose (RP2D) of 4mg/kg in combination with pembrolizumab with 24 evaluable 1L patients (data cutoff of May 1, 2024): ORR of 46% and Disease Control Rate (DCR) of 79% in patients with combined positive score (CPS) ≥1, compared to an ORR of 19% observed with pembrolizumab alone in the historical third-party KEYNOTE-048 trial. This includes one complete response (CR) and 10 partial responses (PR), in addition to eight durable stable diseases (DSD) of >12 weeks....Key data highlights from the CUE-101 expansion portion of the Phase 1b trial evaluating CUE-101 at the RP2D as monotherapy with 20 evaluable 2L+ patients (majority 3L+): mOS of 20.8 months, notably longer than the historical mOS of 7.5 and 8.4 months reported in third-party 2L R/M HNSCC trials: CheckMate 141 and KEYNOTE-040, respectively."

P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Phase 1 Study in Patients With HPV16+ Recurrent/ Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P1 | N=85 | Active, not recruiting | Sponsor: Cue Biopharma | Trial completion date: Dec 2023 ➔ May 2025 | Trial primary completion date: Sep 2023 ➔ Nov 2024

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDKN2A • CTLA4

Cue Biopharma to Present at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - "The presentations will highlight the Company’s Phase 1 trials of its lead interleukin 2 (IL-2)-based biologics, CUE-101 in recurrent/metastatic head and neck cancer and CUE-102 in Wilms’ Tumor 1 positive recurrent/metastatic cancers."

P1 data • Oncology • Squamous Cell Carcinoma of Head and Neck

Three Schedules of CUE-101 Administered Before Surgery or Definitive Chemoradiation Therapy in HLA-A*0201 Positive Patients With Locally Advanced, HPV16-Positive Oropharyngeal Squamous-Cell Carcinoma (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Oct 2025 ➔ Oct 2027 | Trial primary completion date: Oct 2025 ➔ Oct 2027

Metastases • Surgery • Trial completion date • Trial primary completion date • Oncology • Oropharyngeal Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD8 • CDKN2A • IFNG

Cue Biopharma Reports Fourth Quarter and Full Year 2023 Financial Results and Updated Business Highlights (GlobeNewswire) - "Concluded Type B meeting with FDA receiving guidance for potential paths for CUE-101 registrational trials in both monotherapy and combination settings."

FDA event • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Cue Biopharma Reports Fourth Quarter and Full Year 2023 Financial Results and Updated Business Highlights (GlobeNewswire) - P1 | N=85 | NCT03978689 | Sponsor: Cue Biopharma | "Presented notable updates from the ongoing Phase 1 clinical trials of CUE-101...at the 2024 Oppenheimer Annual Healthcare Life Sciences Conference in February: CUE-101 monotherapy in 2L HPV+ R/M HNSCC demonstrated median overall survival (mOS) of 20.8 months vs. historical third-party mOS of 7.5 and 8.4 months with two different CPIs: OPDIVO (nivolumab) and pembrolizumab, respectively. CUE-101 in combination with pembrolizumab in 1L R/M HNSCC showed an overall response rate (ORR) of 46% vs. 19% with pembrolizumab alone in a third-party trial and median progression free survival (mPFS) of 8.3 months vs. 3.2 months with pembrolizumab alone in a third-party trial. CUE-101 continued to demonstrate favorable tolerability in the monotherapy and combination trials."

P1 data • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Cue Biopharma to Host Business Update Call and Webcast (GlobeNewswire) - "Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company developing a novel class of therapeutic biologics to selectively modulate disease-specific T cells, announced today that it will host a conference call and webcast to provide a business update on Monday, April 8, 2024 at 4:30 p.m. EDT...The Company will provide a corporate update highlighting measurable progress advancing its lead clinical oncology programs, CUE-101 and CUE-102..."

Clinical • Oncology