ficerafusp alfa (BCA101) / Biocon - LARVOL DELTA

Ficerafusp alfa 750 mg QW and pembrolizumab in HPV-negative first-line (1L) recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (ESMO Asia 2025) - P1, P2/3 | "Ficerafusp alfa 750 mg QW with pembrolizumab in HPV-neg, PDL-1 CPS ≥1, 1L R/M HNSCC demonstrated sustained clinical efficacy and manageable safety comparable to 1500 mg QW in these preliminary data, establishing a broad therapeutic window. The two doses of this combination are being investigated in the randomized, placebo-controlled, phase 2/3 FORTIFI-HN01 study (NCT06788990)."

Clinical • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • PD-L1 • TGFB1

Bicara Therapeutics’ Preliminary Phase 1b Expansion Cohort Data Evaluating 750mg of Ficerafusp Alfa Weekly Plus Pembrolizumab Advances Pivotal Study Dose Selection on Track for First Quarter 2026 (GlobeNewswire) - "The data were highlighted in an oral presentation by Deborah Wong, MD, PhD of UCLA Medical Center at the European Society for Medical Oncology (ESMO) Asia Congress and will be discussed on a company conference call and webcast today, December 6, at 9:00 a.m. ET....New biomarker data to be presented during Bicara’s corporate call and webcast show that 1500mg of ficerafusp alfa yielded a greater increase TGF-β inhibition within the tumor microenvironment and greater immune activation, compared to 750mg of ficerafusp alfa. The increased TGF-β inhibition in the tumor translated to greater depth of clinical responses at 24 weeks. The median depth of response was 82% at the 1500mg dose vs. 63% at the 750mg dose, and 64% of responders at 1500mg achieved a deep response, compared to 27% of responders at the 750mg dose."

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

Bicara Therapeutics Announces Publication of an Abstract with Preliminary Phase 1b Expansion Cohort Data Evaluating 750mg of Ficerafusp Alfa Weekly Plus Pembrolizumab in 1L HPV-negative R/M HNSCC at ESMO Asia 2025 (GlobeNewswire) - "In the efficacy evaluable population (n=30): 57% (17/30) objective response rate, including 50% (15/30) of patients who achieved a partial response and 7% (2/30) of patients who achieved a complete response; 83% (n=25/30) disease control rate; Complete, prolonged neutralization of TGF-β1 observed. Safety findings were consistent with the known safety profile of ficerafusp alfa plus pembrolizumab in R/M HNSCC."

P1 data • Squamous Cell Carcinoma of Head and Neck

Key Anticipated Upcoming Milestones (GlobeNewswire) - "Present data from a Phase 1b expansion cohort evaluating 750mg of ficerafusp alfa weekly in combination with pembrolizumab in 1L HPV-negative R/M HNSCC patients at the ESMO Asia 2025 Meeting; Present data from a Phase 1b expansion cohort evaluating 2000mg of ficerafusp alfa every other week in combination with pembrolizumab in 1L HPV-negative R/M HNSCC patients in the first quarter of 2026; Present data from a Phase 1b expansion cohort evaluating 1500mg weekly of ficerafusp alfa in combination with pembrolizumab in HPV-negative patients with combined positive scores (CPS) of 0 in 2026; Present data from Phase 1b expansion cohort evaluating ficerafusp alfa both as monotherapy and in combination with pembrolizumab in patients with 3L+ metastatic CRC (RAS/BRAF wild type MSS) in 2026."

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

Dual targeting of TGF-β and EGFR with ficerafusp alfa shows superior anti-tumor activity over cetuximab in KRAS / BRAF wild-type MSS colorectal cancer (SITC 2025) - P1 | "Ficerafusp alfa showed prolonged and significantly improved tumor cytotoxicity (>50%) and a two-fold increase in IFN-γ levels compared to cetuximab (figure 1).Conclusions Ficerafusp alfa showed significantly improved and sustained anti-tumor effects compared to cetuximab in the presence of PBMCs, underscoring the importance of overcoming TGF-β-mediated drug resistance and facilitating immune cell tumor penetration with the TGF-β arm of ficerafusp alfa. This study supports the rationale for evaluation of ficerafusp alfa +/- immunotherapy in the Ph1b expansion cohort for MSS WT KRAS/BRAF mCRC (NCT04429542)."

IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • BRAF • EGFR • IFNG • KRAS • TGFB1

Ficerafusp alfa-driven tumor penetration via EMT and FMT inhibition in the tumor microenvironment (ESMO 2025) - P1 | "The combination of FICERA with pembro in HPV-neg HNSCC paired biopsies from a Ph1b clinical trial or in combination with sotorasib in a preclinical model of resistant lung cancer reveals down-regulation of EMT and enhanced IFN-γ signaling...T-cell responses observed with FICERA alone or in combination are consistent with enhanced immune cell tumor penetration. Orthogonal approaches highlight and support the proposed mechanism of action of the TGF-β arm of FICERA within the TME."

Biomarker • Tumor microenvironment • Head and Neck Cancer • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • CAFs • IFNG • TGFB1

Bicara Therapeutics Inc…announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to ficerafusp alfa (Bicara Press Release) - "... in combination with pembrolizumab for the first line (1L) treatment of patients with metastatic or with unresectable, recurrent (R/M) head and neck squamous cell carcinoma (HNSCC) whose tumors express programmed death-ligand 1 with combined positive score (CPS) ≥1, excluding human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma...BTD was supported by results from multiple Phase 1/1b dose cohorts evaluating ficerafusp alfa in combination with pembrolizumab in patients with 1L HPV-negative R/M HNSCC."

Breakthrough therapy • Squamous Cell Carcinoma of Head and Neck

Bridging EGFR/TGF-β signaling to bypass resistance to immune checkpoint blockade. (PubMed, Clin Cancer Res) - "Although EGFR is a common target in squamous cancers, anti-EGFR monotherapies have shown modest success due to existing or acquired activation of other oncogenic pathways and tumor heterogeneity. A bifunctional fusion protein ficerafusp alfa in combination with pembrolizumab represents a potential solution to overcome resistance in early phase clinical investigation."

Checkpoint inhibition • Journal • Oncology • Squamous Cell Carcinoma • TGFB1

Phase I clinical trial of the bifunctional EGFR/TGF-β fusion protein ficerafusp alfa (BCA101) alone and in combination with pembrolizumab for advanced solid tumors. (PubMed, Clin Cancer Res) - "Ficerafusp alfa exhibited a manageable safety profile and clinical activity as monotherapy and in combination with pembrolizumab, with exposure increasing proportionally at anticipated therapeutic doses."

Journal • P1 data • Dermatitis • Dermatology • Fatigue • Head and Neck Cancer • Hematological Disorders • Immunology • Oncology • Pruritus • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • TGFB1

A multicenter, randomized, double-blind, phase 2/3 study of ficerafusp alfa (BCA101) or placebo in combination with pembrolizumab for first-line treatment of PD-L1-positive, recurrent or metastatic head and neck squamous cell carcinoma: The FORTIFI-HN01 study. (ASCO 2025) - P1, P2/3 | "Secondary endpoints include safety, additional efficacy measures, and patient-reported outcomes (PROs). The trial is actively recruiting, with a planned enrollment of (NCT06788990)."

Clinical • Combination therapy • Metastases • P2/3 data • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • PD-L1 • TGFB1

Ficerafusp alfa with pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: Updated results from an expansion cohort of an open-label, multicenter, phase 1/1b trial. (ASCO 2025) - P1 | "Ficerafusp alfa combined with pembrolizumab continues to show promising efficacy relative to historical data on the current standard of care, particularly in HPV-negative HNSCC. Median PFS and 12-month OS, ORR, and CR rates are encouraging relative to historical benchmarks in pts with HPV-negative HNSCC. 24-month OS and mature OS/DOR outcomes are anticipated."

Clinical • Metastases • P1 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • PD-L1 • TGFB1

Moffitt to Present Plenary and Late-Breaking Data on Blood, Melanoma and Brain Metastases at ASCO 2025 (Newswise) - "Moffitt will be prominently featured at this year’s ASCO Annual Meeting, including a plenary presentation on polycythemia vera. Additional highlights include several oral presentations on melanoma, renal cell carcinoma and head and neck squamous cell carcinoma. Moffitt researchers will also present multiple posters covering a wide range of cancer types, including lung, breast, cervical and biliary tract cancers."

Clinical data • Biliary Tract Cancer • Breast Cancer • Cervical Cancer • Cholangiocarcinoma • Clear Cell Renal Cell Carcinoma • Lung Cancer • Melanoma • Merkel Cell Carcinoma • Polycythemia Vera • Squamous Cell Carcinoma of Head and Neck

Bicara Therapeutics Demonstrates Deep and Durable Responses with Ficerafusp Alfa Plus Pembrolizumab in 1L HPV-Negative R/M HNSCC at ASCO 2025 (GlobeNewswire) - P1/1b | N=292 | NCT04429542 | Sponsor: Bicara Therapeutics | "In the Phase 1/1b trial, ficerafusp alfa in combination with pembrolizumab resulted in deep and durable anti-tumor activity with improved overall survival (OS) compared to historical benchmarks in patients with 1L R/M human papillomavirus (HPV)-negative HNSCC with a PD-L1 combined positive score (CPS) of ≥1 and with at least 24 months of follow-up. In the efficacy evaluable human papillomavirus (HPV)-negative population (n=28): Median duration of response (DOR) of 21.7 months amongst responders (n=15). Median OS of 21.3 months; 2-year OS rate of 46%. 54% (15/28) confirmed objective response rate (ORR); 64% (18/28) ORR, including an additional three unconfirmed responses. 21% (6/28) complete response rate."

P1 data • Squamous Cell Carcinoma of Head and Neck

Bicara Therapeutics Announces Publication of an Abstract with Updated Interim Data from Phase 1/1b Trial of Ficerafusp alfa in 1L R/M HNSCC at the 2025 ASCO Annual Meeting (GlobeNewswire) - P1/1b | N=292 | NCT04429542 | Sponsor: Bicara Therapeutics | "Updated interim data (December 16, 2024 cutoff date) from the Phase 1/1b clinical trial of ficerafusp alfa in patients with 1L R/M HNSCC patients with a PD-L1 combined positive score (CPS) of ≥1. In the efficacy evaluable human papillomavirus (HPV)-negative population (n=28): 64% (18/28) objective response rate, including 21% (6/28) of patients who achieved a complete response. Median progression-free survival was 9.8 months (95% CI: 4.4–23.2) and the 12-month OS rate was 61% (95% CI: 40–76%). Median overall survival (mOS) and median DOR had not been reached yet, with mOS surpassing 20 months."

P1 data • Squamous Cell Carcinoma of Head and Neck

Ficerafusp alfa reverses acquired resistance to the KRAS-G12C inhibitor sotorasib in KRAS-G12C-mutated lung tumors (AACR 2025) - "Recent approvals of KRAS-G12C inhibitors (G12Ci) such as sotorasib (AMG510) and adagrasib have improved treatment responses and overall survival rates2...The combination of sotorasib with ficerafusp alfa resulted in a significant reduction in sotorasib-resistant NCI-H1373 tumors over sotorasib in combination with cetuximab.This study reinforces the hypothesis that TGF-β plays an important role in acquired resistance to G12Ci. Our findings suggest that combining G12Ci with ficerafusp alfa could overcome G12Ci drug-resistance in KRAS-G12C-mutated lung cancer."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • TGFB1

First Quarter 2025 Financial Results (GlobeNewswire) - "Research and development expenses were $34.3 million for the first quarter of 2025 as compared to $12.0 million for the first quarter of 2024. The increase was primarily due to additional costs associated with the initiation of FORTIFI-HN01 a pivotal Phase 2/3 clinical trial, as well as the Company’s ongoing Phase 1/1b clinical trials to advance ficerafusp alfa."

Commercial • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Bicara Therapeutics Reports First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "Ongoing Phase 1/1b Clinical Trial in 1L R/M HNSCC: Updated data with extended follow-up from an ongoing Phase 1/1b trial will be highlighted in an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, which will be held from May 30-June 3, 2025 in Chicago, IL...A cohort evaluating ficerafusp alfa in combination with pembrolizumab in HPV-positive patients with a history of heavy smoking is expected to initiate in 2025....A Phase 1b expansion cohort evaluating ficerafusp alfa both as monotherapy and in combination with pembrolizumab in patients with 3L+ metastatic colorectal cancer (RAS/B-Rapidly Accelerated Fibrosarcoma (BRAF) wild type) is expected to initiate in 2025."

P1 data • Trial status • Colorectal Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

Dual blockade of EGFR and TGF-Β with ficerafusp alfa has the potential to overcome resistance mechanisms in 1L R/M HNSCC in combination with pembrolizumab (AACR 2025) - P1 | "Down-regulation of hypoxia and EMT pathways in both tumor and stromal regions with ficerafusp alfa and P treatment supports the potential role of TGF-β inhibition in preventing the mesenchymal phenotype associated with drug resistance. These findings provide proof of concept that ficerafusp alfa effectively blocks TGF-β signaling in both tumor cells and tumor supporting stromal cells. Association of translational findings with clinical data will be presented."

Combination therapy • IO biomarker • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CAFs • CD8 • CXCL10 • CXCL9 • EGFR • IFNG • TGFB1

Ficerafusp alfa reverses acquired resistance to the KRAS-G12C inhibitor sotorasib in KRAS-G12C-mutated lung tumors (GlobeNewswire) - "Bicara Therapeutics...announced multiple presentations related to ficerafusp alfa at the American Association for Cancer Research (AACR) Annual Meeting 2025....In in vitro and in vivo preclinical studies, ficerafusp alfa + a KRAS-G12C inhibitor (G12Ci) was shown to be more effective than G12Ci alone, with G12Ci-resistant lung cancer cells remaining susceptible to this combination. This presentation supports the hypothesis that TGF-β inhibition by ficerafusp alfa helps reverse G12Ci resistance and highlights the potential of combining G12Ci with ficerafusp alfa in drug-resistant KRAS-G12C-mutated cancers, including lung cancer."

Preclinical • Non Small Cell Lung Cancer

Dose expansion results of single agent ficerafusp alfa (BCA101), a bifunctional EGFR/TGF-β inhibitor in patients with metastatic or advanced cutaneous squamous cell carcinoma (cSCC) (GlobeNewswire) - P1 | N=292 | NCT04429542 | Sponsor: Bicara Therapeutics | "Bicara Therapeutics...announced multiple presentations related to ficerafusp alfa at the American Association for Cancer Research (AACR) Annual Meeting 2025....As of the data cut-off date of March 20, 2025, the single-arm, multicenter dose expansion cohort from an ongoing Phase 1/1b trial evaluating ficerafusp alfa monotherapy enrolled 23 patients with 2L+ metastatic or advanced cutaneous squamous cell carcinoma (cSCC) who had received (or been intolerant to or ineligible for) prior anti–PD-1 therapy....The overall response rate (ORR) was 30.4% (7/23 patients) and the clinical benefit rate (complete response, partial response, and stable disease lasting for ≥5 weeks) was 82.6% (19/23 patients). Median progression-free survival (mPFS) was 7.0 months (95% CI, 2.7-8.9 months), and the PFS rate at 12 months was 25.4%, demonstrating improvements over historical treatment in cSCC."

P1 data • Squamous Cell Skin Cancer

Dual blockade of EGFR and TGF-β with ficerafusp alfa has the potential to overcome resistance mechanisms in 1L R/M HNSCC in combination with pembrolizumab (GlobeNewswire) - "Bicara Therapeutics...announced multiple presentations related to ficerafusp alfa at the American Association for Cancer Research (AACR) Annual Meeting 2025....Preliminary findings from a translational medicine biomarker dataset from Bicara’s ongoing Phase 1/1b trial of ficerafusp alfa in 1L (first line) recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) demonstrate that ficerafusp alfa effectively blocks TGF-β signaling in the tumor and prevents key mechanisms associated with drug resistance. Spatial transcriptomics revealed downregulation of epithelial-mesenchymal transition and hypoxia pathways in human papillomavirus (HPV)-negative tumors with ficerafusp alfa and pembrolizumab...Complementary clinical data highlighting enhanced durability in HPV-negative R/M HNSCC to be presented at the 2025 American Society of Clinical Oncology Annual Meeting."

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

Dose expansion results of single agent ficerafusp alfa (BCA101), a bifunctional EGFR/TGFβ inhibitor in patients with metastatic or advanced cutaneous squamous cell carcinoma (CSCC) (AACR 2025) - "Ficerafusp alfa was well tolerated and demonstrated encouraging single agent activity in CSCC patients previously treated with anti-PD1. Further investigation of ficerafusp alfa in pts with metastatic or advanced CSCC alone and in combination with immunotherapy is warranted. Updated data will be presented."

Clinical • Metastases • Non-melanoma Skin Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • TGFB1

Bicara Therapeutics to Present Updated Data from Ongoing Phase 1/1b Trial of Ficerafusp alfa in 1L R/M HNSCC at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (GlobeNewswire) - "Bicara Therapeutics...announced that updated data from the company’s ongoing Phase 1/1b clinical trial of ficerafusp alfa in 1L (first line) recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) will be highlighted in an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting....Details of the oral presentation are as follows: Title: Ficerafusp alfa with pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: Updated results from an expansion cohort of an open-label, multicenter, phase 1/1b trial; Abstract #: 6017."

P1 data • Squamous Cell Carcinoma of Head and Neck

Ficerafusp alfa reverses acquired resistance to the KRAS-G12C inhibitor sotorasib in KRAS-G12C-mutated lung tumors (GlobeNewswire) - "Bicara Therapeutics announces upcoming presentations at AACR Annual Meeting 2025....Published Abstract #: 4434....This presentation will highlight a preclinical dataset that provides insights into the role of inhibiting TGF-β in overcoming acquired KRAS-G12C-inhibitor drug-resistant KRAS-G12C-mutated lung cancer."

Preclinical • Non Small Cell Lung Cancer

Dual blockade of EGFR and TGF-β with ficerafusp alfa has the potential to overcome resistance mechanisms in 1L R/M HNSCC in combination with Pembrolizumab (GlobeNewswire) - "Bicara Therapeutics announces upcoming presentations at AACR Annual Meeting 2025....Published Abstract #: 3284....This presentation will highlight a translational medicine biomarker dataset that provides insights into the effects of targeted inhibition of TGF-β with ficerafusp alfa."

Biomarker • Squamous Cell Carcinoma of Head and Neck