BNT327 / BioNTech - LARVOL DELTA

First report of efficacy and safety results from a phase 2 trial evaluating BNT327/PM8002 plus chemotherapy (chemo) as first-line treatment (1L) in unresectable malignant mesothelioma. (ASCO 2025) - P2 | " After a safety run-in (n=6), this ongoing, multicenter, single-arm phase 2 clinical trial recruited chemo naive pts (pts) aged ≥18 yrs with unresectable malignant mesothelioma (pleural (MPM) or peritoneal (MPeM)) to evaluate BNT327 30 mg/kg Q3W IV combined with 4-6 cycles pemetrexed and platinum, followed by BNT327 maintenance. BNT327 plus chemo as a 1L regimen for mesothelioma showed encouraging efficacy, including in tumors of epithelioid histology. AEs were consistent with those expected for the treatment regimen."

Clinical • P2 data • Anemia • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Renal Disease • Solid Tumor • Thoracic Cancer

A global phase 2/3, randomized, open-label trial of BNT327/PM8002 in combination with chemotherapy (chemo) in first-line (1L) non-small cell lung cancer (NSCLC). (ASCO 2025) - P2/3 | "In the Phase 3 part, pts will be randomized 1:1 to receive BNT327 at the selected dose (based on the Phase 2 part) plus chemo (carboplatin + pemetrexed for Substudy A, carboplatin + paclitaxel for Substudy B) or pembrolizumab 200 mg plus chemo Q3W IV, followed by Q3W IV maintenance BNT327 or pembrolizumab (both with maintenance pemetrexed for Substudy A). Secondary endpoints include duration of response, disease control rate (Phase 2), PFS per investigator, ORR, landmark PFS and OS, patient reported outcomes and occurrence of AEs, and rates of dose interruption, reduction and discontinuation due to TEAEs (Phase 3); with efficacy endpoints per RECIST 1.1; safety per CTCAE v5.0. The trial is enrolling."

Clinical • Combination therapy • IO biomarker • P2/3 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

A global phase III, double-blind, randomized trial of BNT327/PM8002 plus chemotherapy (chemo) compared to atezolizumab plus chemo in patients (pts) with first-line (1L) extensive-stage small cell lung cancer (ES-SCLC). (ASCO 2025) - P3 | "Preliminary results from a Phase II trial showed encouraging efficacy results and a manageable safety profile for BNT327 with paclitaxel as second-line (2L) treatment of pts with SCLC (1992P, ESMO 2023)...Pts will be initially randomized 1:1:1 to receive combination therapy of atezolizumab (1,200 mg IV) plus chemo (etoposide + carboplatin) (Arm 1), BNT327 (2,000 mg IV) plus chemo (Arm 2), or BNT327 (1,400 mg IV) plus chemo (Arm 3) administered Q3W for four cycles, followed by maintenance therapy with atezolizumab (Arm 1) or BNT327 (Arm 2 and Arm 3) Q3W until confirmed disease progression, intolerable toxicity, participant withdrawal, trial termination or up to two years, whichever occurs first...Secondary endpoints include progression-free survival (PFS), objective response rate, PFS rates and OS rates at defined timepoints, patient-reported outcomes, occurrence of treatment emergent adverse event (TEAEs) and occurrence of dose delay, infusion interruption, and..."

Clinical • P3 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

BNT327/PM8002 Plus Chemo Is Active in Unresectable Pleural and Peritoneal Mesothelioma (OncLive) - P2 | N=55 | NCT05918107 | Sponsor: Biotheus Inc. | "The first-line combination of the investigational bispecific antibody BNT327/PM8002 plus chemotherapy elicited durable responses in patients with unresectable pleural and peritoneal mesothelioma, according to initial data from a phase 2 trial (NCT05918107/CTR20221048), which were presented at the 2025 ASCO Annual Meeting. At a data cutoff of March 28, 2025, and a median follow-up of 22.3 months for patients in the total population (n = 31), the confirmed overall response rate (cORR) was 51.6% (95% CI, 33.1%-69.9%), including 1 complete response (CR), 15 partial responses (PRs), 12 instances of stable disease (SD), and 2 instances of progressive disease (PD). The disease control rate (DCR) was 90.3% (95% CI, 74.3%-98.0%). Among patients in the total population with epithelioid histology (n = 19), the cORR was 47.4% (95% CI, 24.5%-71.1%), and the DCR was 89.5% (95% CI, 66.9%-98.7%)."

P2 data • Peritoneal Mesothelioma • Pleural Mesothelioma

BioNTech and Bristol Myers Squibb Announce Global Strategic Partnership to Co-Develop and Co-Commercialize Next-generation Bispecific Antibody Candidate BNT327 Broadly for Multiple Solid Tumor Types (The Manila Times) - "BioNTech SE...and Bristol Myers Squibb...announced that the companies have entered into an agreement for the global co-development and co-commercialization of BioNTech's investigational bispecific antibody BNT327 across numerous solid tumor types. Under the agreement, BioNTech and BMS will work jointly to broaden and accelerate the development of this clinical candidate....A global Phase 3 trial evaluating the candidate in triple negative breast cancer ('TNBC') is planned to start by the end of 2025....Under the terms of the agreement, the companies will jointly develop and commercialize BNT327, including the development of BNT327 as monotherapy and in combination with other products. Both companies have the right to independently develop BNT327 in further indications and combinations, including combinations of BNT327 with proprietary pipeline assets."

Licensing / partnership • Non Small Cell Lung Cancer • Small Cell Lung Cancer • Triple Negative Breast Cancer

BioNTech to Present Progress Across Diversified Oncology Pipeline at the 2025 ASCO Annual Meeting (The Manila Times) - "Three presentations on BNT327...will detail data from ongoing later-stage and potentially registrational clinical trials: An oral presentation will feature the first data from a Phase 2 clinical trial...of BNT327 in combination with chemotherapy as first-line treatment for patients with unresectable malignant mesothelioma. Malignant mesothelioma is a type of cancer that develops in the tissue that covers the lung or the abdomen. The preliminary data indicated anti-tumor activity and a manageable safety profile. Two posters will detail the ongoing global Phase 3 and Phase 2/3 clinical trials, ROSETTA Lung-01...in extensive-stage small cell lung cancer ('ES-SCLC') and ROSETTA Lung-02...in non-small cell lung cancer ('NSCLC')."

P2 data • Trial status • Mesothelioma • Non Small Cell Lung Cancer • Small Cell Lung Cancer

Dual PD-L1 blockade and VEGF-A neutralization with the bispecific antibody BNT327/PM8002 shows potent antitumor activity in preclinical models (CIMT 2025) - "Antitumor activity was dose-dependent where tested, and superior to single PD-1 (pembrolizumab) or PD-L1 (atezolizumab) checkpoint inhibitor treatment. The safety and efficacy of BNT327 is being investigated in multiple clinical trials in patients with solid tumors, including Phase II and Phase III trials investigating the combination with chemotherapeutic agents in triple-negative breast cancer and lung cancer. Phase I/II trials investigating the combination of BNT327 with antibody-drug conjugates have also been initiated."

Preclinical • Breast Cancer • Colon Cancer • Colorectal Cancer • Lung Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • IFNG • IL2

Discovery of HX016-7, a novel PD-L1 x VEGF BsAb, as a new candidate treatment of solid tumors (AACR 2025) - "A first-in-class PD-L1xVEGF bispecific antibody (BsAb), BNT327/PM8002, has demonstrated promising efficacy in treating TNBC and NSCLC cancers in advance stage of clinical development, which prompted us to engineer a novel and potentially best-in-class (BIC) PD-L1xVEGF BsAb by using a validated anti-PD-L1 and a novel anti-VEGF (HX006, a novel VEGF mAb with more favor activity over Avastin) mAb sequences. In a subcutaneous A549 non-small-cell lung cancer (NSCLC) cell-derived xenograft model in immunocompromised mice, HX016-7 also showed slightly stronger anti-tumor activity over BNT327/PM8002, which can be attributed to anti-VEGF function. We believe these preclinical data warrants the candidacy of HX016-7 to be further developed for the treatment of solid tumors."

Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • PD-L1

A Clinical Study to Find the Optimal Dose of an Investigational Treatment Called BNT323 When Used in Combination With Another Investigational Treatment, BNT327, and to Test if That Combination Treatment is Safe and Beneficial for Patients With Advanced Breast Cancer (clinicaltrials.gov) - P1/2 | N=320 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • Oncology • Solid Tumor

A Clinical Study to Investigate the Efficacy and Safety of an Investigational Combination Therapy With BNT324 and BNT327 in Patients With Advanced Lung Cancer (clinicaltrials.gov) - P1/2 | N=594 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

BioNTech Announces First Quarter 2025 Financial Results and Corporate Update (GlobeNewswire) - P1/2a | N=1,123 | NCT05438329 | Sponsor: DualityBio Inc. | "Interim data from the ongoing Phase 1/2 clinical trial (NCT05438329) evaluating BNT327 with BNT325/DB-1305, a TROP2-targeting ADC candidate being developed in collaboration with Duality Biologics (Suzhou) Co. Ltd. ('DualityBio', in patients with advanced/metastatic solid tumors showed a manageable safety profile and early signs of anti-tumor activity in a cohort with patients with platinum-resistant ovarian cancer ('PROC'). Across the 13 efficacy evaluable patients with PROC, seven patients achieved partial response and three stable disease. Responses were also observed in patients with non-small cell lung cancer ('NSCLC') or triple-negative breast cancer ('TNBC')."

P1/2 data • Platinum resistant • Non Small Cell Lung Cancer • Ovarian Cancer • Triple Negative Breast Cancer

Activity of BNT327/PM8002 (PD-L1 x VEGF-A bispecific antibody) in combination with BNT325/DB-1305 (TROP2 ADC) in solid tumors: Early preclinical and clinical evidence to support BNT327 + ADC combinations (AACR 2025) - P1/2 | "Emerging data suggest that IO-ADC combinations may lead to better patient outcomes. Early clinical data showed successful dose escalation allowing enrollment to NSCLC, TNBC, ovarian, and cervical cancer expansion cohorts, with updated clinical data planned to be presented. Further evaluation is ongoing of BNT327 with ADCs against HER2 (BNT323/DB-1303), B7H3 (BNT324/DB-1311) and HER3 (BNT326/YL202), with a focus on tumors where early monotherapy efficacy has been observed with these ADCs."

Combination therapy • IO biomarker • Preclinical • Breast Cancer • Cervical Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • B2M • CD276 • ERBB3 • HER-2

DB-1311 in Combination With BNT327 or DB-1305 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P2 | N=440 | Not yet recruiting | Sponsor: DualityBio Inc.

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

BNT327-02: Safety and Preliminary Effectiveness of BNT327, an Investigational Therapy for Breast Cancer, When Given in Combination With Chemotherapy (clinicaltrials.gov) - P2 | N=70 | Recruiting | Sponsor: BioNTech SE | Trial completion date: Jan 2027 ➔ Sep 2028 | Trial primary completion date: Mar 2025 ➔ Nov 2027

Trial completion date • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

BioNTech Announces First Quarter 2025 Financial Results and Corporate Update (GlobeNewswire) - "First data from an ongoing Phase 2 clinical trial (NCT05918107) in first-line mesothelioma and two trial-in-progress posters for the ongoing global Phase 3 and Phase 2/3 clinical trials, ROSETTA Lung-01 (NCT06712355) and ROSETTA Lung-02 (NCT06712316) respectively, will be presented at the American Society for Clinical Oncology ('ASCO') Annual Meeting taking place from May 30 to June 3, 2025 in Chicago, Illinois."

P2 data • Trial status • Mesothelioma • Non Small Cell Lung Cancer • Small Cell Lung Cancer

BioNTech will present preclinical data characterizing the mode of action of BNT327 (GlobeNewswire) - "BNT327 is an investigational next-generation bispecific antibody combining PD-L1 checkpoint inhibition with VEGF-A neutralization. BNT327 showed a high binding affinity to PD-L1 and VEGF-A and efficient blocking of PD-1/PD-L1 and VEGF-A/VEGFR2 signaling. Anti-tumor activity superior to single PD-1/PD-L1 blockade or anti-VEGF-A treatment was observed in multiple tumor models."

Preclinical • Solid Tumor

Dual PD-L1 blockade and VEGF-A neutralization with the bispecific antibody BNT327/PM8002 shows potent antitumor activity in preclinical models (AACR 2025) - "Antitumor activity was dose-dependent where tested, and superior to single PD-1 (pembrolizumab) or PD-L1 (atezolizumab) checkpoint inhibitor treatment. In conclusion, BNT327 inhibits PD-1/PD-L1 signaling and VEGF-A/VEGFR2 signaling in vitro and shows potent antitumor activity in vivo both in syngeneic and xenograft models. The safety and efficacy of BNT327 as a monotherapy or in combination is being investigated in multiple clinical trials in patients with solid tumors, including Phase II and Phase III trials investigating the combination with chemotherapeutic agents in triple-negative breast cancer and lung cancer."

Preclinical • Breast Cancer • Colon Cancer • Colorectal Cancer • Lung Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • IFNG • IL2

BNT327-01: Safety, Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Small-cell Lung Cancer in Combination With Chemotherapy (clinicaltrials.gov) - P2 | N=110 | Active, not recruiting | Sponsor: BioNTech SE | Trial completion date: Aug 2026 ➔ May 2028 | Trial primary completion date: Mar 2025 ➔ Jun 2027

Trial completion date • Trial primary completion date • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

BioNTech to Present Clinical Data Updates Across mRNA and Immunomodulatory Oncology Portfolio at ESMO Congress 2024 (GlobeNewswire) - "Updates on several Phase 2 and Phase 1/2 clinical trials evaluating BNT327/PM8002 in various indications as monotherapy and in combination with chemotherapy will be presented. BNT327/PM8002 is an investigational bispecific antibody combining PD-L1 checkpoint inhibition with VEGF-A neutralization for vascular normalization and immunostimulation in the microenvironment of the tumor. Two oral presentations and one poster will provide clinical data updates for cohorts with advanced non-small cell lung cancer ('NSCLC'), locally advanced/metastatic triple-negative breast cancer ('TNBC') and advanced renal cell carcinoma. BNT327/PM8002 is being developed in collaboration with Biotheus Inc."

P1/2 data • P2 data • Breast Cancer • Genito-urinary Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Triple Negative Breast Cancer

A Study of PM8002 (Anti-PD-L1/VEGF) in Combination With Chemotherapy in Patients With NSCLC (clinicaltrials.gov) - P2 | N=64 | Active, not recruiting | Sponsor: Biotheus Inc. | Phase classification: P2/3 ➔ P2 | N=374 ➔ 64 | Trial primary completion date: Mar 2025 ➔ Sep 2024

Enrollment change • Phase classification • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BNT327 With Chemotherapy Elicits Strong Results in ES-SCLC (Targeted Oncology) - P2 | N=50 | NCT05844150 | Sponsor: Biotheus Inc. | "The PD-L1 and VEGF-A bispecific antibody BNT327 demonstrated encouraging clinical activity and had a tolerable safety profile when combined with chemotherapy as a first-line treatment in extensive-stage small cell lung cancer (ES-SCLC), according to a phase 2 trial (NCT05844150) presented at the 2025 European Lung Cancer Congress (ELCC)....The median treatment exposure was 5.7 months (95% CI, 4.4-7.2). At a median follow-up of 14.5 months (95% CI, 13.4-15.3), the confirmed overall response rate (ORR) was 85.4% (95% CI, 72.2%-93.9%) and the unconfirmed ORR was 87.5% (95% CI, 74.8%-95.3%). The disease control rate (DCR) was 97.9% (95% CI, 88.9%-100%). The 6-month and 12-month OS rates were 91.7% (95% CI, 79.3%-96.8%) and 72.7% (95% CI, 57.6%-83.1%), respectively. The median OS was not yet mature."

P2 data • Small Cell Lung Cancer

Updated phase II efficacy and safety results of BNT327/PM8002 combined with paclitaxel as second-line (2L) therapy in small cell lung cancer (SCLC) (ELCC 2025) - P2 | "Funding: Biotheus Inc. BNT327 shows clinical activity as 2L treatment in SCLC, with adverse events consistent with chemo and IO treatment. Further evaluation in 2L SCLC is ongoing in a global phase II and a phase III trial in China and with BNT324/DB-1311, a B7H3 ADC, in a phase I/II study."

Clinical • P2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD276

A Clinical Study to Investigate the Efficacy and Safety of an Investigational Combination Therapy With BNT324 and BNT327 in Patients With Advanced Lung Cancer (clinicaltrials.gov) - P1/2 | N=594 | Not yet recruiting | Sponsor: BioNTech SE

New P1/2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Safety and Preliminary Effectiveness of BNT327, an Investigational Therapy for Patients With Non-small Cell Lung Cancer in Combination With Chemotherapy Following Chemoimmunotherapy (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Phase 2 study of the efficacy and safety of BNT327/PM8002 plus systemic chemotherapy as first-line therapy for extensive-stage small-cell lung cancer (ES-SCLC) (ELCC 2025) - P2 | "Combined targeting of PD-L1 and angiogenesis with chemotherapy may enhance anti-tumor immune responses vs standard of care.We present data from an ongoing phase II study of BNT327, an investigational bispecific antibody targeting PD-L1 and VEGF-A, plus chemotherapy in first-line ES-SCLC. This open label, single arm, multicenter phase II study (NCT05844150) recruited pts aged ≥18 years with ECOG PS 0-1 with histologically or cytologically confirmed SCLC who had not received systemic treatment for ES-SCLC, to evaluate tumor responses per RECIST 1.1 and safety per CTCAE v5.0 of 30 mg/kg Q3W BNT327 plus platinum-etoposide administered Q3W for 4 cycles, followed by BNT327 Q3W until disease progression or unacceptable toxicity. As of 21 Nov 2023, 50 pts had been enrolled (median age 59 years, range 46–75, 80% ECOG 1). BNT327 plus platinum-based chemotherapy as a first-line treatment for ES-SCLC showed encouraging efficacy and an acceptable tolerability profile and is..."

Clinical • P2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor