PF-06804103 / Pfizer - LARVOL DELTA

PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors (clinicaltrials.gov) - P1 | N=95 | Terminated | Sponsor: Pfizer | Completed ➔ Terminated; The trial was terminated based on the stage in drug development and assessment of PF-06804103 relative to the leading external competition. The decision was not due to a safety concern.

Trial termination • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Safety and Tolerability of a Novel Anti-HER2 Antibody-Drug Conjugate (PF-06804103) in Patients With HER2-Expressing Solid Tumors: A Phase 1 Dose Escalation Study. (PubMed, Mol Cancer Ther) - P1 | "Safety and efficacy were dose-dependent. Clinical trial registration: clinicaltrials.gov NCT03284723."

Journal • P1 data • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Keratitis • Musculoskeletal Pain • Ocular Inflammation • Oncology • Ophthalmology • Pain • Solid Tumor

Safety, tolerability, pharmacokinetics, and antitumor activity of SHR-A1811 in HER2-expressing/mutated advanced solid tumors: A global phase 1, multi-center, first-in-human study (AACR 2023) - "Background: SHR-A1811 is an ADC comprised of a humanized anti-HER2 monoclonal antibody (trastuzumab), a cleavable linker, and a DNA topoisomerase I inhibitor payload. SHR-A1811 was well-tolerated and showed promising antitumor activity in heavily pretreated advanced solid tumors.Table 1. Subgroup analyses of ORRNo. of prior treatment lines in metastatic setting in all pts (N=250)HER2 positive BC (N=108)HER2-low BC (N=77)Other tumor types (N=65)≤381.8% (45/55)58.7% (27/46)36.7% (18/49)>381.1% (43/53)51.6% (16/31)31.3% (5/16)Prior anti-HER2 therapies in pts with BC (N=185)*HER2 positive BC (N=108)HER2-low BC (N=77)All BC (N=185)Any82.2% (88/107, 73.7-89.0)68.8% (11/16, 41.3-89.0)80.5% (99/123, 72.4-87.1)Trastuzumab81.9% (86/105, 73.2-88.7)75.0% (9/12, 42.8-94.5)81.2% (95/117, 72.9-87.8)Pertuzumab83.0% (39/47, 69.2-92.4)100% (5/5, 47.8-100)84.6% (44/52, 71.9-93.1)Pyrotinib86.9% (53/61, 75.8-94.1)71.4% (5/7, 29.0-96.3)85.3% (58/68, 74.6-92.7)Lapatinib80.0% (28/35,..."

Clinical • Metastases • P1 data • PK/PD data • Biliary Cancer • Biliary Tract Cancer • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Urothelial Cancer • HER-2

Emerging new treatments in HER2 positive breast cancer (SG-BCC 2023) - P1 | "Trastuzumab deruxtecan (T-DXd) was approved in December 2022 by the FDA for patients with pretreated HER2- positive breast cancer based on the results of the phase III trial Destiny-Breast03 [3], showing an impressive improvement in progression-free survival with an hazard ratio of 0.33 (95% CI 0.26– 0.43, p-value<0.0001) compared to T-DM1, according to the last update presented at SABCS 2022 [4]...Besides T-DXd and SYD985, other ADCs have been or are under investigation, including, but not limited to, patritumab deruxtecan, disitamab vedotin, XMT-1522, MM-302, MEDI-4276, A166, ARX788, BAT8001 and PF-06804103...Several TKIs have been successfully developed, with tucatinib being the latest to enter clinical practice based on the results of the HER2CLIMB trial [7], with particular importance for patients with brain metastases. Other promising emerging treatments targeting HER2/3 receptors are the HER2- targeted bispecific antibodies (including, among others, KN026..."

IO biomarker • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Immune Modulation • Oncology • Solid Tumor • CDK4 • ER • HER-2 • KLRC1 • PD-L1 • PIK3CA

PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors (clinicaltrials.gov) - P1; N=106; Completed; Sponsor: Pfizer; Recruiting ➔ Completed

Trial completion • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

[VIRTUAL] A phase I dose escalation study evaluating the safety and tolerability of a novel anti-HER2 antibody-drug conjugate (PF‑06804103) in patients with HER2-positive solid tumors. (ASCO 2020) - P1 | "Background: PF-06804103 is an anti-HER2 immunoglobulin G1 antibody-drug conjugate (ADC), comprising an anti-HER2 monoclonal antibody conjugated with a cleavable linker to the cytotoxic agent Aur0101. The PF-06804103 ADC demonstrated manageable toxicity and promising anti-tumor activity in this small, heavily pretreated study population. Research Funding: Pfizer"

Clinical • P1 data • Alopecia • Breast Cancer • Dermatopathology • Fatigue • Gastric Cancer • Gastrointestinal Cancer • Gene Therapies • HER2 Breast Cancer • Oncology • Pain • Solid Tumor

Messersmith Makes Sense of the Novel Approaches on the Rise in GI Malignancies (OncLive) - "The heterogeneity of tumors in GI cancers continues to pose a challenge, according to Messersmith. As such, understanding how circulating tumor DNA will play into the management of patients as RAS inhibitors emerge in the clinic will be an area of interest going forward, Messersmith added."

Media quote

PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors (clinicaltrials.gov) - P1; N=148; Recruiting; Sponsor: Pfizer; Active, not recruiting ➔ Recruiting; N=50 ➔ 148

Clinical • Enrollment change • Enrollment open • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors (clinicaltrials.gov) - P1; N=40; Active, not recruiting; Sponsor: Pfizer; Recruiting ➔ Active, not recruiting; N=148 ➔ 40

Clinical • Enrollment change • Enrollment closed • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors (clinicaltrials.gov) - P1; N=148; Recruiting; Sponsor: Pfizer; Trial completion date: Mar 2024 ➔ Aug 2021; Trial primary completion date: Mar 2024 ➔ Aug 2021

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors (clinicaltrials.gov) - P1; N=148; Recruiting; Sponsor: Pfizer; Trial completion date: Nov 2023 ➔ Feb 2024; Trial primary completion date: Nov 2023 ➔ Feb 2024

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors (clinicaltrials.gov) - P1; N=148; Recruiting; Sponsor: Pfizer; Trial completion date: Mar 2023 ➔ Nov 2023; Trial primary completion date: Mar 2023 ➔ Nov 2023

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors (clinicaltrials.gov) - P1; N=148; Recruiting; Sponsor: Pfizer; Trial completion date: May 2022 ➔ Mar 2023; Trial primary completion date: May 2022 ➔ Mar 2023

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors (clinicaltrials.gov) - P1; N=148; Recruiting; Sponsor: Pfizer; Trial completion date: Sep 2021 ➔ May 2022; Trial primary completion date: Sep 2021 ➔ May 2022

Clinical • Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

PF-06804103, a site-specific anti-HER2 antibody-drug conjugate for the treatment of HER2-expressing breast, gastric, and lung cancers. (PubMed, Mol Cancer Ther) - "The approval of ado-trastuzumab emtansine (T-DM1) in HER2+ metastatic breast cancer validated HER2 as a target for HER2-specific antibody-drug conjugates (ADC). Herein, we showcase our platform approach in optimizing ADC design resulting in the generation of the anti-HER2 ADC PF-06804103. The design elements of identifying novel sites of conjugation employed in this study serve as a platform for developing optimized ADCs against other tumor-specific targets."

Journal • Breast Cancer • Gastric Cancer • HER2 Breast Cancer • Lung Cancer • Oncology • Solid Tumor

Use of translational modeling and simulation for quantitative comparison of PF-06804103, a new generation HER2 ADC, with Trastuzumab-DM1. (PubMed, J Pharmacokinet Pharmacodyn) - "The models were translated to human and suggested greater efficacy for PF-06804103 compared to T-DM1. In conclusion, a fit-for-purpose translational PK/PD strategy for ADCs is presented and used to compare a new generation HER2 ADC with T-DM1."

Journal • Oncology • HER-2

New data from 18 approved and investigational Pfizer medicines to be showcased at ASCO20 Virtual Scientific Program (Businesswire) - "Pfizer Inc...today announced that new data from clinical trials of 18 approved and investigational medicines will be presented virtually at the ASCO20 Virtual Scientific Program, from May 29-May 31. The data that will be presented build on Pfizer’s strong track record in oncology by providing new insights in areas like breast, colorectal and genitourinary cancers, which include bladder, prostate, and kidney cancer."

Clinical data • P1 data • Bladder Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Renal Cell Carcinoma • Solid Tumor • Urothelial Cancer

PF-06804103 Dose Escalation in HER2 Positive Solid Tumors (clinicaltrials.gov) - P1; N=124; Recruiting; Sponsor: Pfizer; N=95 ➔ 124

Clinical • Enrollment change