trastuzumab pamirtecan (BNT323) / DualityBio, BioNTech - LARVOL DELTA

BioNTech and DualityBio Announce Phase 3 Trial of ADC Candidate BNT323/DB-1303 Met Primary Endpoint of Progression Free Survival in HER2-Positive Metastatic or Unresectable Breast Cancer (BioNTech Press Release)

P3 data • HER2 Positive Breast Cancer

BNT323-03: A Phase 1/2 trial of BNT323/DB-1303 (HER2 ADC) with BNT327 (PD-L1 x VEGF-A) in patients (pts) with advanced breast cancer (BC) (ESMO 2025) - No abstract available

Clinical • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PD-L1 • VEGFA

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=380 | Recruiting | Sponsor: BioNTech SE | Trial completion date: Sep 2032 ➔ May 2029

Trial completion date • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

ENGOT- en25: A Clinical Study of the Anti-cancer Effects of an Investigational Therapy or Chemotherapy in Patients With Recurring Uterine Cancer (clinicaltrials.gov) - P3 | N=504 | Recruiting | Sponsor: BioNTech SE | Not yet recruiting ➔ Recruiting

Enrollment open • Endometrial Cancer • Oncology • Solid Tumor • Uterine Cancer

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

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

ENGOT- en25: A Clinical Study of the Anti-cancer Effects of an Investigational Therapy or Chemotherapy in Patients With Recurring Uterine Cancer (clinicaltrials.gov) - P3 | N=504 | Not yet recruiting | Sponsor: BioNTech SE | Trial completion date: Aug 2029 ➔ Jan 2030 | Trial primary completion date: Oct 2027 ➔ Mar 2028

Trial completion date • Trial primary completion date • Endometrial Cancer • Oncology • Solid Tumor • Uterine Cancer

BioNTech Announces Fourth Quarter and Full Year 2024 Financial Results and Corporate Update (GlobeNewswire) - "BNT323/DB-1303 is being evaluated in a Phase 1/2 clinical trial (NCT05150691) in patients with advanced/unresectable, recurrent or metastatic HER2-expressing solid tumors. Data from patients with HER2-expressing (IHC3+, 2+, 1+ or ISH-positive) advanced endometrial carcinoma are expected in 2025. A confirmatory Phase 3 clinical trial (NCT06340568) is planned to start in 2025. Preparation of a potential Biologics License Application ('BLA') submission for BNT323/DB-1303 as a second line or subsequent therapy in HER2-expressing advanced endometrial cancer in 2025....BNT211: A pivotal Phase 2 clinical trial in patients with testicular germ cell tumors is expected to start in 2025 based on encouraging clinical activity observed in this patient population in the ongoing Phase 1 clinical trial."

FDA filing • New P2 trial • P1/2 data • Trial status • Endometrial Cancer • Testicular Cancer

BioNTech Announces Fourth Quarter and Full Year 2024 Financial Results and Corporate Update (GlobeNewswire) - "First clinical data from the ongoing global Phase 1/2 expansion cohorts (NCT05438329) evaluating the combination of BNT327 and BNT325/DB-1305, a TROP2-targeted antibody-drug conjugate ('ADC') candidate, are planned to be published in 2025. Additional clinical trials exploring novel combinations of BNT327 with the ADC candidates BNT323/DB-1303 (trastuzumab pamirtecan) targeting HER2, BNT324/DB-1311 targeting B7-H3 or BNT326/YL202 targeting HER3 are planned to start in 2025."

New trial • P1/2 data • Oncology • Solid Tumor

A Study of DB-1303/BNT323 vs Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Metastatic Breast Cancer (DYNASTY-Breast02) (clinicaltrials.gov) - P3 | N=532 | Recruiting | Sponsor: DualityBio Inc. | Trial primary completion date: Dec 2025 ➔ May 2026

Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • PGR

Trastuzumab Pamirtecan (DB-1303/BNT323) In Patients With Previously Treated HER2-Expressing Advanced/Metastatic Endometrial Cancer: First Clinical Data From A Global Phase 2 Study [WITHDRAWN] (ESGO 2025) - No abstract available

Clinical data • Metastases • P2 data • Endometrial Cancer • Oncology • Solid Tumor • HER-2

ENGOT- en25: A Clinical Study of the Anti-cancer Effects of an Investigational Therapy or Chemotherapy in Patients With Recurring Uterine Cancer (clinicaltrials.gov) - P3 | N=468 | Not yet recruiting | Sponsor: BioNTech SE | Trial completion date: Mar 2029 ➔ Aug 2029 | Initiation date: Jan 2025 ➔ Jun 2025 | Trial primary completion date: May 2027 ➔ Oct 2027

Trial completion date • Trial initiation date • Trial primary completion date • Endometrial Cancer • Oncology • Solid Tumor • Uterine Cancer

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 | Not yet recruiting | Sponsor: BioNTech SE

New P1/2 trial • Breast Cancer • Oncology • Solid Tumor

BioNTech Provides Business and Pipeline Updates at 43rd Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "A global randomized Phase 3 clinical trial evaluating BNT327/PM8002 in first line triple-negative breast cancer ('TNBC') is on track to start in 2025. Plan to initiate additional clinical trials exploring novel combinations of BNT327/PM8002 with ADCs BNT323/DB-1303 (trastuzumab pamirtecan), BNT324/DB-1311 and BNT326/YL202 in 2025. Plan to present first clinical data from the ongoing global Phase 1/2 expansion cohorts (NCT05438329) evaluating BNT327/PM8002 plus BNT325/DB-1305 in multiple solid tumors in 2025. Plan to present clinical data from the ongoing global Phase 2 dose optimization trials evaluating BNT327/PM8002 plus chemotherapy in advanced TNBC (NCT06449222) and first line SCLC (NCT06449209) in 2025."

New P3 trial • New trial • P2 data • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer

BioNTech Provides Business and Pipeline Updates at 43rd Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "Interim data from an ongoing global randomized Phase 2 clinical trial (NCT04486378) evaluating autogene cevumeran compared to watchful waiting in adjuvant ctDNA+ stage II (high risk) / stage III colorectal cancer ('CRC') are anticipated in late 2025 or 2026....Plan to present clinical data from an ongoing Phase 1/2a trial (NCT05150691) evaluating BNT323/DB-1303 in HER2-expressing advanced endometrial cancer in 2025. Preparation of a potential Biologics License Application ('BLA') submission for BNT323/DB-1303 as a second line or subsequent therapy in HER2-expressing advanced endometrial cancer​ in 2025. Plan to initiate a global Phase 3 confirmatory clinical trial (NCT06340568) evaluating BNT323/DB-1303 in advanced endometrial cancer in 2025."

FDA filing • P1/2 data • P2 data • Trial status • Colorectal Cancer • Endometrial Cancer

BioNTech Announces Third Quarter 2024 Financial Results and Corporate Update (BioNTech Press Release) - "BNT323/DB-1303 is being evaluated in a Phase 1/2 clinical trial (NCT05150691) in patients with advanced/unresectable, recurrent or metastatic HER2-expressing solid tumors. A potentially registrational cohort of patients with HER2-expressing (IHC3+, 2+, 1+ or ISH-positive) advanced/recurrent endometrial carcinoma has completed enrollment. Data from this cohort are expected in 2025; A confirmatory Phase 3 trial (NCT06340568) in patients with advanced endometrial cancer is in planning; A pivotal Phase 3 trial (DYNASTY-Breast02; NCT06018337) is being conducted in patients with Hormone Receptor-positive ('HR+') and HER2-low metastatic breast cancer that progressed on hormone therapy and/or Cyclin-Dependent Kinase 4/6 ('CDK4/6') inhibition.....Topline data from the ongoing Phase 3 trial in HR+ and HER2-low metastatic breast cancer that have progressed on hormone therapy and/or CDK4/6 inhibition are expected in 2026."

Clinical data • Trial status • Breast Cancer • Endometrial Cancer • HER2 Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Duality plans Hong Kong IPO to fund trials of BioNTech-partnered ADCs and beyond (FierceBiotech) - "The biotech named two BioNTech-partnered ADCs as 'core products.' One of the products, known as both DB-1303 and BNT323, is a HER2-directed ADC that Duality said could be ready to file for accelerated approval as early as 2025....The IPO filing reveals details of the biotech’s activities, such as the fact BioNTech has paid $21 million in milestones tied to DB-1303 and the potential problems it is facing."

Commercial • FDA filing • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

ENGOT- en25: A Clinical Study of the Anti-cancer Effects of an Investigational Therapy or Chemotherapy in Patients with Recurring Uterine Cancer (clinicaltrials.gov) - P3 | N=468 | Not yet recruiting | Sponsor: BioNTech SE | Trial completion date: Dec 2028 ➔ Mar 2029 | Initiation date: Aug 2024 ➔ Nov 2024

Trial completion date • Trial initiation date • Endometrial Cancer • Oncology • Solid Tumor • Uterine Cancer

DYNASTY-Breast02: A phase III trial of BNT323/DB-1303 vs investigator's choice chemotherapy in HER2-low, hormone receptor positive, metastatic breast cancer (ESMO 2024) - P1/2, P3 | "The phase 1 NCT05150691 trial showed promising antitumor responses in HER2 low BC patients (unconfirmed overall response rate 38.5%, n=5/13) alongside a favorable toxicity profile across 85 pts with advanced/metastatic solid tumors, with no dose limiting toxicities observed up to 10 mg/kg (ASCO 2023 abstract #3023).Trial design: Dynasty-Breast02 (NCT06018337) is a phase 3, 1:1 randomized, multi-center, open-label trial comparing BNT323/DB-1303, dosed intravenously Q3W as monotherapy at 8 mg/kg, to physician's choice of chemotherapy (capecitabine, paclitaxel or nab-paclitaxel). The primary analysis will occur after approximately 337 events. Enrollment is currently open."

Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CTSC • HER-2

A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors (clinicaltrials.gov) - P1/2 | N=766 | Recruiting | Sponsor: DualityBio Inc. | Trial completion date: Oct 2025 ➔ Oct 2027 | Trial primary completion date: Jun 2025 ➔ Apr 2026

Metastases • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • HER-2

BioNTech Announces Second Quarter 2024 Financial Results and Corporate Update (GlobeNewswire) - "BNT323/DB-1303 is being evaluated in a Phase 1/2 clinical trial (NCT05150691) in patients with advanced/unresectable, recurrent or metastatic HER2-expressing solid tumors. A potentially registrational cohort with HER2-expressing (IHC3+, 2+, 1+ or ISH-positive) patients with advanced/recurrent endometrial carcinoma has completed enrollment. Data from this cohort are expected in 2025. A confirmatory Phase 3 trial (NCT06340568) in patients with advanced endometrial cancer is planned to start in 2024....Topline data from the ongoing Phase 3 trial in HR+ and HER2-low metastatic BC that have progressed on hormone therapy and/or CDK4/6 inhibition are expected as early as 2025."

P1/2 data • P3 data: top line • Trial initiation date • Breast Cancer • Endometrial Cancer • Gynecologic Cancers • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

A Patient With Metastatic Uterine Carcinosarcoma With Presumed Pneumonitis Secondary to Investigational Drug Db-1303, an Antibody-Drug Conjugate Comprised of Anti-HER2 Monoclonal Antibody Linked to a DNA Topoisomerase I Inhibitor (ATS 2024) - "Treatment with piperacillin/tazobactam and azithromycin and prednisone 40mg PO daily was commenced...Due to concern of drug-induced pneumonitis from her trial medication, steroid therapy was changed to to methylprednisolone 1mg/kg daily with trimethoprim/sulfamethoxazole prophylaxis...Day 9, after a multidisciplinary discussion, she was given infliximab (weight-based 5mg/kg) with continuation of methylprednisolone 2mg/kg daily...For this case, we based out treatment decisions on the published guidelines for management of pneumonitis induced by fam-trastuzumab-deruxtecan-nxki - another ADC targeting HER2. Clinicians should be aware of pneumonitis as a potential side effect of ADCs. Moreover, this case highlights the need for further research into management and prevention of ADC-induced pneumonitis."

Clinical • Metastases • Asthma • Colorectal Cancer • Cough • Immunology • Oncology • Pneumonia • Sarcoma • Solid Tumor • Uterine Cancer

A Clinical Study of the Anti-cancer Effects of an Investigational Therapy or Chemotherapy in Patients With Recurring Uterine Cancer (clinicaltrials.gov) - P3 | N=468 | Not yet recruiting | Sponsor: BioNTech SE | Trial completion date: Aug 2028 ➔ Dec 2028 | Initiation date: Apr 2024 ➔ Aug 2024 | Trial primary completion date: Oct 2026 ➔ Feb 2027

Trial completion date • Trial initiation date • Trial primary completion date • Endometrial Cancer • Oncology • Solid Tumor • Uterine Cancer

BioNTech Announces First Quarter 2024 Financial Results and Corporate Update (GlobeNewswire) - "A confirmatory Phase 3 trial (NCT06340568) in this patient population is planned to start in 2024....A multicenter, open-label, first-in-human Phase 1 clinical trial (NCT05653752) evaluating BNT326/YL202 as a later-line treatment in patients with locally advanced or metastatic epidermal growth factor receptor ('EGFR')-mutated non-small cell lung cancer ('NSCLC') or HR+/HER2-negative breast cancer is ongoing in the United States and China. Preliminary data from this study are expected to be presented at the 2024 ASCO Annual Meeting."

P1 data • Trial status • Breast Cancer • Endometrial Cancer • Gynecologic Cancers • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Uterine Cancer

The maximum support amount is 5 billion, and many provinces and cities have introduced policies to support pharmaceutical innovation; China Biopharma has introduced a variety of pipelines [Google translation] (163.com) - "On April 8, according to the CDE official website, Ingen Biotech’s DB-1303 for injection was approved for clinical use and is intended to be used for HER2-positive unresectable/metastatic breast cancer."

New trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor