ficerafusp alfa (BCA101) / Biocon, Bicara Therapeutics - LARVOL DELTA

A multicenter, randomized, double-blind, Phase 2/3 study of ficerafusp alfa (BCA101) or placebo in combination with pembrolizumab for first-line (1L) treatment of PD-L1-positive, recurrent or metastatic (R/M) HPV-negative head and neck squamous cell carcinoma (HNSCC): The FORTIFI- HN01 study (FHNO 2026) - No abstract available

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

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

Dose expansion results of the bifunctional EGFR/TGFβ inhibitor BCA101 with pembrolizumab in patients with recurrent, metastatic head and neck squamous cell carcinoma. (ASCO 2023) - P1 | "Stage 1 of this dose expansion cohort of BCA101+P shows encouraging anti-tumor activity with additive potential, particularly among HPV-neg pts; and the combination is well tolerated among this R/M HNSCC population. Further investigation is warranted. Study funded by Bicara Therapeutics and conducted in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc."

Clinical • Metastases • Anemia • Head and Neck Cancer • Hematological Disorders • Immune Modulation • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1 • TGFB1

Preliminary phase 1/1b dose expansion results of the bifunctional EGFR/TGFβ inhibitor ficerafusp alfa (BCA101) with pembrolizumab in patients with squamous cell carcinoma of the anal canal. (ASCO-GI 2025) - P1 | "The addition of ficerafusp alfa demonstrated encouraging efficacy, with increased ORR, DCR, and 12-month PFS relative to historical precedent with pembrolizumab alone. Safety and tolerability were acceptable. Further investigation of this combination in pts with advanced SCAC is warranted."

Clinical • P1 data • Anal Carcinoma • Gastrointestinal Cancer • Oncology • TGFB1

FORTIFI-FLEX: A Study Evaluating Ficerafusp Alfa (BCA101) QW in Combination With Pembrolizumab vs Alternative Ficerafusp Alfa Dosing in 1L R or M HNSCC (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: Bicara Therapeutics

New P2 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

A multicenter, randomized, double-blind, Phase 2/3 study of ficerafusp alfa (BCA101) or placebo in combination with pembrolizumab for first-line (1L) treatment of PD-L1-positive, recurrent or metastatic (R/M) HPV-negative head and neck squamous cell carcinoma (HNSCC): FORTIFI-HN01 (ESMO 2026) - No abstract available

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

Ficerafusp Alfa, Pembrolizumab, and Stereotactic Body Radiotherapy (SBRT) for Head and Neck Squamous Cell Carcinoma (HNSCC) (clinicaltrials.gov) - P1/2 | N=45 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Aug 2033 ➔ Nov 2033 | Initiation date: Jun 2026 ➔ Sep 2026 | Trial primary completion date: Aug 2028 ➔ Nov 2028

Trial completion date • Trial initiation date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Key Anticipated Upcoming Milestones (Bicara Press Release) - "HNSCC: Continued to enroll Phase 3 of the FORTIFI-HN01 pivotal trial in 1L R/M HPV-negative HNSCC and expect to be substantially enrolled by the end of the year to enable topline results from an interim analysis in mid-2027. Other Solid Tumors, Including mCRC: Present data from Phase 1b expansion cohort evaluating ficerafusp alfa both as monotherapy and in combination with pembrolizumab in patients with 3L+ mCRC (RAS/BRAF wild type MSS) in the second half of 2026."

Enrollment status • P1 data • P3 data: top line • Colorectal Cancer • Squamous Cell Carcinoma of Head and Neck

Ficerafusp alfa: “FICERA has the potential to significantly expand the HPV-negative HNSCC market“ (Bicara Therapeutics) - Corporate Presentation

Commercial • Oncology • Squamous Cell Carcinoma of Head and Neck

Ficerafusp Alfa in 1L R/M HPV-Negative HNSCC (Bicara Press Release) - "Initiated FORTIFI-FLEX, a randomized, open-label, clinical study that will evaluate ficerafusp alfa in combination with pembrolizumab, administered as a 12-week loading dose of 1500mg weekly (QW) followed by maintenance dosing of 2250mg every three weeks (Q3W). The company expects to have results from this study by the time of a potential U.S. accelerated approval in 1L R/M HPV-negative HNSCC."

Trial status • Squamous Cell Carcinoma of Head and Neck

HPV Status Shapes the Therapeutic Rationale for Bispecific Antibodies in R/M HNSCC (EACR 2026) - "Amivantamab, Petosemtamab, Ivonescimab, and Ficerafusp alfa are emerging targeted bispecific/bifunctional antibodies under investigation... This study provides biological validation of bispecific and bifunctional antibody use in R/M HNSCC setting. In particular, we identified that the therapeutic benefit is correlated to HPV status. In the future, survival analysis will be integrated in order to validate this data."

Bispecific • IO biomarker • Head and Neck Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • TGFB1 • TGFBR2

A multicenter, randomized, double-blind, phase 2/3 study of ficerafusp alfa (BCA101) or placebo in combination with pembrolizumab for first-line treatment of HPV-negative, PD-L1–positive, recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): FORTIFI-HN01. (ASCO 2026) - P1, P2/3 | "Secondary endpoints include safety, duration of response, progression free survival, clinical benefit rate, and patient-reported outcomes. The trial is actively recruiting, with planned enrollment of ~650 subjects."

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

The impact of depth of response on long-term clinical outcomes: Exploratory analyses from multiple expansion cohorts of a phase 1/1b study of ficerafusp alfa plus pembrolizumab in first-line recurrent/metastatic (R/M) HPV-negative head and neck carcinoma (HNSCC). (ASCO 2026) - P1 | "Ficerafusp alfa plus pembrolizumab demonstrated deep responses across multiple dose levels. Deep responses were associated with improved long-term efficacy outcomes, including DOR, PFS, and OS. This suggests that depth of response may represent a clinically meaningful surrogate for understanding long-term efficacy outcomes in HPV-negative HNSCC."

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

Depth and durability of response with TGF-β trapping in recurrent or metastatic (R/M) HPV-negative head and neck squamous cell carcinoma (HNSCC): Long-term results from two expansion cohorts of a phase 1/1b study of ficerafusp alfa plus pembrolizumab. (ASCO 2026) - P1, P2/3 | "Deeper and more durable tumor responses were observed with ficerafusp alfa 1500 mg vs 750 mg. Exposure and PD markers of TGF-β inhibition demonstrated dose-related trends consistent with mechanism of action. Together, these data suggest that TGF‑β inhibition with ficerafusp alfa facilitates T-cell infiltration, enhancing immunologic activity, contributing to deep and durable responses for patients with HPV-neg HNSCC."

IO biomarker • Metastases • P1 data • Fibrosis • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1 • TGFB1

Ficerafusp Alfa Plus Pembrolizumab Demonstrated Differentiated Three-Year Overall Survival and Deep Responses Driven by TGF-β Inhibition in 1L R/M HPV-Negative HNSCC (GlobeNewswire) - "The data will be presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting....At a median follow-up of three years, 1500mg of ficerafusp alfa weekly in combination with pembrolizumab demonstrated an estimated 31% overall survival, approximately doubling OS compared to a retrospective analysis of standard of care. Phase 1b dataset of ~90 patients in 1L R/M HPV-negative HNSCC across all three doses demonstrated that deep responses translated into durable long-term outcomes across DOR, PFS, and OS, with a generally well-tolerated safety profile and no new safety signals."

P1 data • Squamous Cell Carcinoma of Head and Neck

Recent highlights and breakthroughs in immunotherapy for head and neck cancers. (PubMed, Curr Opin Oncol) - "Recent advances highlight a rapid surge in positive immunotherapy trials across different head and neck cancer entities, with clinical benefit observed both when immune checkpoint inhibitors are moved earlier in the disease course and when they are combined with agents targeting resistance mechanisms or enabling more precise drug delivery to tumors."

IO biomarker • Journal • Head and Neck Cancer • Nasopharyngeal Carcinoma • Non-melanoma Skin Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Thyroid Gland Anaplastic Carcinoma • Thyroid Gland Carcinoma • BRAF

First Quarter 2026 Highlights and Recent Progress (GlobeNewswire) - "Continued strong execution in FORTIFI-HN01, our pivotal trial in 1L HPV-negative R/M HNSCC; expect to be substantially enrolled by the end of the year to enable an interim analysis in mid-2027 to support potential accelerated approval. Based on recent discussions with the U.S. Food and Drug Administration (FDA), the company plans to initiate a randomized clinical study that will evaluate ficerafusp alfa in combination with pembrolizumab, administered as a 12-week loading dose of 1500mg weekly (QW) followed by maintenance dosing of 2250mg every three weeks (Q3W). The company expects to initiate the study in the third quarter of 2026 to have results in time for potential U.S. accelerated approval."

Enrollment status • FDA event • New trial • P2/3 data • Squamous Cell Carcinoma of Head and Neck

Immunotherapeutic strategies in HPV-positive and HPV-negative recurrent/metastatic oropharyngeal squamous cell carcinoma: from PD-1 blockade to EGFR-directed bispecifics and therapeutic HPV vaccines. (PubMed, Crit Rev Oncol Hematol) - "Emerging agents such as ficerafusp alfa, petosemtamab, and amivantamab have demonstrated promising early clinical activity, particularly in biomarker-enriched or post-immunotherapy settings. In HPV-positive disease, therapeutic vaccines targeting E6/E7 oncoproteins have shown encouraging immunogenicity and preliminary antitumor activity, especially when combined with PD-1 blockade. Overall, the immunotherapeutic landscape of OPSCC is evolving toward a biomarker-driven framework integrating viral status, immune contexture and pathway activation to enable more precise and personalized treatment strategies."

IO biomarker • Journal • Review • Oncology • Oropharyngeal Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • TGFB1

Ficerafusp Alfa (BCA101) With Pembrolizumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Two-Year Results of an Expansion Cohort of a Phase I/Ib Trial. (PubMed, J Clin Oncol) - P1 | "Ficerafusp alfa plus pembrolizumab demonstrated favorable safety and tolerability with promising antitumor activity in the first-line treatment of R/M HNSCC, particularly in those with HPV-negative tumors."

First-in-human • Journal • P1 data • Dermatitis • Dermatology • Head and Neck Cancer • Hematological Disorders • Immunology • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • PD-L1

FORTIFI-HN01: A Study of Ficerafusp Alfa (BCA101) or Placebo in Combination With Pembrolizumab in First-Line PD-L1-pos, R or M HNSCC (clinicaltrials.gov) - P2/3 | N=650 | Recruiting | Sponsor: Bicara Therapeutics | N=216 ➔ 650

Enrollment change • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Ficerafusp Alfa, Pembrolizumab, and Stereotactic Body Radiotherapy (SBRT) for Head and Neck Squamous Cell Carcinoma (HNSCC) (clinicaltrials.gov) - P1/2 | N=45 | Not yet recruiting | Sponsor: Washington University School of Medicine

New P1/2 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

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

N'FORCE: Phase II Study of Ficerafusp Alfa in Combination With Nivolumab in Patients With Platinum-refractory Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=131 | Not yet recruiting | Sponsor: Groupe Oncologie Radiotherapie Tete et Cou

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

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