ficerafusp alfa (BCA101) / Biocon - LARVOL DELTA

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

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) - "Bicara Therapeutics announces upcoming presentations at AACR Annual Meeting 2025....Published Abstract #: CT034....This presentation will highlight data from a Phase 1/1b dose expansion cohort of ficerafusp alfa monotherapy in second line or later cSCC patients."

P1 data • Squamous Cell Skin Cancer

Bicara Therapeutics Announces First Patients Enrolled in FORTIFI-HN01, a Pivotal Phase 2/3 Clinical Trial of Ficerafusp Alfa in 1L Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (GlobeNewswire) - "Bicara Therapeutics...announced the first patients have been enrolled in FORTIFI-HN01, a pivotal Phase 2/3 trial of ficerafusp alfa in combination with pembrolizumab in 1L (first line) recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)....FORTIFI-HN01 is a global, randomized, double-blinded, placebo-controlled, pivotal Phase 2/3 trial that aims to enroll approximately 650 R/M HNSCC patients, excluding patients with human papillomavirus (HPV)-positive with oropharyngeal squamous cell carcinoma. Patients enrolled in the trial must have a PD-L1 CPS greater than or equal to one, and not have received systemic therapy in the R/M setting."

Trial status • Squamous Cell Carcinoma of Head and Neck

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

New P2/3 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Bicara Therapeutics Presents Phase 1/1b Dose Expansion Results with Ficerafusp Alfa in Advanced Squamous Cancer of the Anal Canal at the 2025 ASCO Gastrointestinal Cancers Symposium (GlobeNewswire) - P1/1b | N=292 | NCT04429542 | Sponsor: Bicara Therapeutics | "Presentation Highlights: As of the data cut-off date of December 5, 2024, the single-arm, multicenter dose expansion cohort from an ongoing Phase 1/1b trial evaluated ficerafusp alfa in combination with pembrolizumab in 28 patients with immune checkpoint inhibitor-naive SCAC that was locally advanced/unresectable or metastatic, and who had received 1-2 prior lines of chemotherapy; The confirmed overall response rate was 25.0% (7/28 patients), irrespective of PD-L1 CPS score, including 6 partial responses (PR) and 1 complete response. In addition to the confirmed responses, there was 1 patient pending a confirmed PR; Median progression-free survival (PFS) was 2.9 months and the PFS rate at 12 months was 40.7% (27 evaluable patients)."

P1 data • Anal Carcinoma • Squamous Cell Carcinoma

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

Bicara Therapeutics Reports Third Quarter 2024 Financial Results and Provides Business Update (GlobeNewswire) - "The Company has aligned with the U.S. Food and Drug Administration on the design of FORTIFI-HN01, a pivotal Phase 2/3 trial of ficerafusp alfa in combination with pembrolizumab in 1L (first line) recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) and expects to initiate the trial late in the fourth quarter of 2024 or early in the first quarter of 2025...Data from a Phase 1b expansion cohort evaluating ficerafusp alfa in combination with pembrolizumab in second line (2L) or later squamous cancer of the anal canal is expected at a medical meeting in the first quarter of 2025; Updated data from a Phase 1b expansion cohort evaluating ficerafusp alfa monotherapy in 2L or later cutaneous squamous cell carcinoma is expected at a medical meeting in the first half of 2025...Research and development expenses were $15.9 million....The increase was primarily due to additional costs associated with the Company’s ongoing clinical trials to advance ficerafusp alfa."

Clinical data • New P2/3 trial • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Advancements in TGF-β Targeting Therapies for Head and Neck Squamous Cell Carcinoma. (PubMed, Cancers (Basel)) - "While preclinical data have demonstrated the great anti-tumorigenic potential of TGF-β inhibitors, the underwhelming results of ongoing and completed clinical trials highlight the difficulty actualizing these benefits into clinical practice. This topical review will discuss the relevant preclinical and clinical findings for TGF-β inhibitors in HNSCC and will explore the potential role of patient stratification in the development of this therapeutic strategy."

Journal • Review • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TGFB1

Bicara Therapeutics Reports Updated Interim Phase 1/1b Data of Ficerafusp Alfa (BCA101) in 1L HPV-negative Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) (Businesswire) - P1 | N=292 | KEYNOTE-E28 (NCT04429542) | Sponsor: Bicara Therapeutics | "28 patients were HPV-negative and 11 patients were HPV-positive, as determined by p16 testing. 54% ORR in total evaluable study population (21/39 patients), including 3 unconfirmed responses. 15% complete response (CR) rate (6/39 patients). 26% (10/39) of patients with 100% reductions in target lesions. Favorable tolerability profile with the most common treatment-related adverse events (TRAEs) including acneiform rash (76%, with majority being Grade 1/2 in severity), fatigue (43%), and hypophosphatemia (38%). In HPV-negative population (n=28): 64% ORR (18/28 patients) with responses observed across different levels of PD-L1 expression, including 3 unconfirmed responses. 18% complete response (CR) rate (5/28 patients). 29% (8/28) of patients with 100% reductions in target lesions. Median progression free survival (mPFS) of 9.8 months."

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

KEYNOTE-E28: Study of Safety and Tolerability of BCA101 Monotherapy and in Combination Therapy in Patients With EGFR-driven Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=292 | Recruiting | Sponsor: Bicara Therapeutics | Trial completion date: Jun 2025 ➔ Jun 2027 | Trial primary completion date: Dec 2024 ➔ Dec 2026

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Anal Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oropharyngeal Cancer • Ovarian Cancer • Pancreatic Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • PD-L1