calotatug ginistinag (XMT-2056) / Mersana, GSK - LARVOL DELTA

XMT-2056, a HER2-Directed STING Agonist Antibody-Drug Conjugate, Induces Innate Anti-Tumor Immune Responses by Acting on Cancer Cells and Tumor-Resident Immune Cells. (PubMed, Clin Cancer Res) - "These data provide a robust preclinical characterization of XMT-2056 and provide rationale and strategy for its clinical testing."

IO biomarker • Journal • Oncology • HER-2

XMT-2056, a HER2-Directed STING Agonist Antibody-Drug Conjugate, Induces Innate Anti-Tumor Immune Responses by Acting on Cancer Cells and Tumor-Resident Immune Cells (Clin Cancer Res) - "XMT-2056 achieved tumor-targeted delivery of the STING agonist upon systemic administration in mice and induced innate anti-tumor immune responses; single dose administration of XMT-2056 induced tumor regression in a variety of tumor models with high and low HER2 expression. Notably, XMT-2056 demonstrated superior efficacy and reduced systemic inflammation compared to a free STING agonist. XMT-2056 exhibited concomitant immune-mediated killing of HER2-negative cells specifically in the presence of HER2-positive cancer cells, supporting the potential for activity against tumors with heterogenous HER2 expression."

Preclinical • Solid Tumor

Mersana Therapeutics Provides Business Update and Announces Fourth Quarter and Full Year 2024 Financial Results (GlobeNewswire) - "XMT-2056: Mersana has continued to advance the dose escalation portion of its Phase 1 clinical trial of XMT-2056, the company's lead Immunosynthen ADC candidate targeting a novel HER2 epitope....Mersana plans to continue enrolling patients in dose escalation and expects to present initial clinical pharmacodynamic STING activation data for XMT-2056 in 2025."

P1 data • Trial status • Oncology

Mersana’s Expected 2025 Milestones and Areas of Focus (GlobeNewswire) - "Emi-Le: 1H2025: Continue enrollment in expansion at a dose of 67.4 mg/m2 Q4W in patients with TNBC who have previously received at least one prior topo-1 ADC; 2025: Initiate enrollment in expansion at a second dose in patients with TNBC who have previously received at least one prior topo-1 ADC; 2025: Present additional Phase 1 clinical data from dose escalation and backfill cohorts. XMT-2056, Mersana’s lead Immunosynthen ADC targeting a novel HER2 epitope: 2025: Present initial clinical pharmacodynamic STING activation data."

Clinical data • Enrollment status • P1 data • Triple Negative Breast Cancer

Mersana Therapeutics Provides Business Update and Announces Third Quarter 2024 Financial Results (GlobeNewswire) - "Recent Accomplishments, Strategic Priorities and Expected Milestones...- XMT-2056: Mersana continues to escalate dosing in its Phase 1 clinical trial of XMT-2056, the company’s lead Immunosynthen ADC candidate targeting a novel HER2 epitope....At the Society for Immunotherapy of Cancer (SITC) 2024 Annual Meeting last week, Mersana presented new preclinical data demonstrating XMT-2056’s ability to activate STING signaling and inhibit tumor growth at very low doses."

Preclinical • Trial status • Colorectal Cancer • Gastric Cancer • HER2 Positive Breast Cancer • Non Small Cell Lung Cancer

XMT-2056, a HER2-targeted immunosynthen STING agonist antibody-drug conjugate, induces anti-tumor activity at low doses in preclinical models (SITC 2024) - P1 | "We further demonstrate that XMT-2056, when administered to mice at very low doses, activates STING signaling in tumors and upregulates immune pathway genes, including PD-L1, resulting in significant tumor growth inhibition. Conclusions Together, these results underscore the therapeutic potential of XMT-2056 in treating tumors with various levels of HER2-expression and support its ongoing clinical exploration in a Phase 1 dose escalation study in patients with solid tumors expressing HER2 (NCT05514717)."

IO biomarker • Preclinical • Oncology • Solid Tumor • HER-2 • PD-L1

XMT-2056: a phase 1 study of a HER2-directed STING agonist antibody drug conjugate (ADC) in HER2+ solid tumors (SITC 2024) - P1 | "The trial is open for enrollment. NCT05514717."

IO biomarker • P1 data • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2

Mersana Therapeutics Provides Business Update and Announces Second Quarter 2024 Financial Results (GlobeNewswire) - "XMT-2056: Mersana continues to enroll patients in the dose escalation portion of its Phase 1 clinical trial of XMT-2056, the company’s lead Immunosynthen ADC candidate targeting a novel HER2 epitope....Research and development (R&D) expenses for the second quarter of 2024 were $17.2 million, compared to $49.0 million for the same period in 2023. Included in R&D expenses for the second quarter of 2024 were $2.4 million in non-cash stock-based compensation expenses. The year-over-year decline in R&D expenses was primarily related to reduced costs associated with manufacturing and clinical activities for UpRi, a discontinued ADC candidate..."

Commercial • Trial status • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Mersana Therapeutics Provides Business Update and Announces First Quarter 2024 Financial Results (GlobeNewswire) - "XMT-2056: The company plans to advance dose escalation in this trial in 2024."

Trial status • Oncology • Solid Tumor

A Study of XMT-2056 in Advanced/Recurrent Solid Tumors That Express HER2 (clinicaltrials.gov) - P1 | N=162 | Recruiting | Sponsor: Mersana Therapeutics | Suspended ➔ Recruiting | Trial completion date: Nov 2025 ➔ Apr 2027 | Trial primary completion date: Nov 2025 ➔ Apr 2027

Enrollment open • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Mersana Therapeutics Provides Business Update and Announces Fourth Quarter and Full Year 2023 Financial Results (GlobeNewswire) - "At the European Society of Gynaecological Oncology (ESGO) 2024 Congress from March 7-10, 2024 in Barcelona, Spain, clinical data will be presented for Mersana’s two discontinued NaPi2b ADC product candidates: XMT-1536 (UpRi), which was developed using the company’s first-generation Dolaflexin ADC platform, and XMT-1592, which was developed using the company’s next-generation Dolasynthen ADC platform....The decline in R&D expenses was primarily related to reduced manufacturing and clinical costs related to UpRi and XMT-2056 and manufacturing costs for the company’s Dolasynthen platform, partially offset by increased clinical costs related to XMT-1660."

Clinical data • Commercial • Oncology • Solid Tumor

Mersana Therapeutics Announces Business Updates, Expected 2024 Milestones and Upcoming Presentation at the 42nd Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "XMT-1660: Mersana continues to advance its Phase 1 clinical trial of XMT-1660, the company’s lead Dolasynthen ADC candidate targeting B7-H4...Mersana plans to initiate tumor-specific expansion cohorts in the second quarter of 2024 and share initial dose escalation and backfill cohort data in mid-2024...XMT-2056: Mersana is restarting its Phase 1 clinical trial of XMT-2056...The company plans to advance dose escalation in 2024....In the first half of 2024, Mersana expects to present data at multiple scientific meetings demonstrating Dolasynthen’s differentiation from first-generation cytotoxic ADC platforms. The presentations will include clinical data from two discontinued ADC candidates, XMT-1592 and XMT-1536 (UpRi)."

Clinical data • P1 data • Trial status • Oncology • Solid Tumor

Mersana Therapeutics Provides Business Update and Announces Third Quarter 2023 Financial Results (GlobeNewswire) - ".Additionally, we are now preparing to resume enrollment in our Phase 1 clinical trial of XMT-2056, a novel HER2-directed STING-agonist ADC product candidate....Advance XMT-1660 and Mersana’s Dolasynthen Platform: Mersana expects to complete the dose escalation portion of this Phase 1 clinical trial by the end of 2023 and initiate the dose expansion portion of the trial in 2024."

Trial status • Oncology • Solid Tumor

Mersana Therapeutics Announces FDA has Lifted Clinical Hold on Phase 1 Clinical Trial of XMT-2056 (GlobeNewswire) - "Mersana Therapeutics...announced that the U.S. Food and Drug Administration (FDA) has lifted the clinical hold on the company’s Phase 1 clinical trial of XMT-2056....'We have lowered the starting dose in our Phase 1 dose escalation design. We are pleased to have aligned with FDA on the path forward....The multicenter Phase 1 open-label trial is investigating XMT-2056 in previously treated patients with advanced/recurrent solid tumors expressing HER2, including breast, gastric, colorectal and non-small-cell lung cancers."

FDA event • Breast Cancer • Colorectal Cancer • Gastric Cancer • Non Small Cell Lung Cancer

Tumor-Targeted Activation of the STING Pathway with Immunosynthen ADCs (PEGS 2023) - "XMT-2056 is a HER2-targeted Immunosynthen ADC that binds a novel HER2 epitope and has entered clinical development. The mechanistic translational studies presented could guide clinical development."

Oncology • HER-2 • STING

XMT-2056, a HER2-targeted STING agonist antibody-drug conjugate, exhibits ADCC function that synergizes with STING pathway activation and contributes to anti-tumor responses (AACR 2023) - "The ADCC activity of HT-19 was comparable to that of trastuzumab in NK cell co-cultures. Collectively, our data reveal a synergy between ADCC function and STING pathway induction both mediated by XMT-2056, which enhances the cancer cell-killing activity of FcγRIII+ cells. This additional mechanism of action of XMT-2056 can potentially impact the overall anti-tumor immune responses in tumors infiltrated by FcγRIII+ cells."

Oncology • GZMB • HER-2 • IFNG • NCAM1

"Did anyone ask @marc_drcell about the clinical results of XMT-2056, or was discussion only on preclin? #AACR23 @AACR" (@GooseData)

Clinical • Oncology

"Wow! #AACR23! Over 100 posters on best target #Her2. Many are promising ADCs like Xmt-2056 and innovative intrinsic TI payloads like Eribulin. What is everyone most excited to see?!?! 👀" (@GooseData)

Oncology

A Study of XMT-2056 in Advanced/Recurrent Solid Tumors That Express HER2 (clinicaltrials.gov) - P1 | N=171 | Suspended | Sponsor: Mersana Therapeutics | Recruiting ➔ Suspended

Metastases • Trial suspension • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Mersana Therapeutics Announces Clinical Hold on XMT-2056 Phase 1 Clinical Trial (GlobeNewswire) - "Mersana Therapeutics, Inc...announced that the Phase 1 trial of XMT-2056 has been placed on clinical hold by the U.S. Food and Drug Administration (FDA). This action follows the company’s communication to FDA that Mersana was voluntarily suspending the trial due to a recent Grade 5 (fatal) serious adverse event (SAE) that was deemed to be related to XMT-2056. The SAE and its cause remain under investigation."

Trial suspension • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Mersana Therapeutics Announces Initiation of Phase 1 Trial of XMT-2056 in HER2-Expressing Tumors (GlobeNewswire) - "Mersana Therapeutics...announced the initiation of patient dosing in its Phase 1 clinical trial of XMT-2056, the company’s lead Immunosynthen product candidate....XMT-2056 is a systemically administered Immunosynthen STING agonist ADC that is designed to target a novel HER2 epitope and locally activate STING signaling in both tumor-resident immune cells and in tumor cells to provide the potential to treat patients with HER2-high or -low tumors as monotherapy or in combination with standard-of-care agents....The multicenter Phase 1 open-label trial will investigate XMT-2056 in previously treated patients with advanced/recurrent solid tumors expressing HER2, including breast, gastric, colorectal and non-small-cell lung cancers."

Trial status • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • HER-2

Mersana Therapeutics Provides Business Update and Announces Strategic Objectives and Expected Milestones (GlobeNewswire) - "Expected Milestones: XMT-1660: Complete dose escalation portion of Phase 1 clinical trial in 2023; XMT-2056: Initiate Phase 1 clinical trial in the first quarter of 2023."

Trial status • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Fallopian Tube Cancer • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • Triple Negative Breast Cancer

A Study of XMT-2056 in Advanced/Recurrent Solid Tumors That Express HER2 (clinicaltrials.gov) - P1 | N=144 | Recruiting | Sponsor: Mersana Therapeutics | Not yet recruiting ➔ Recruiting | Initiation date: Sep 2022 ➔ Dec 2022

Enrollment open • Trial initiation date • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Mersana Therapeutics Provides Business Update and Announces Third Quarter 2022 Financial Results (GlobeNewswire) - "Strategic Goals, Recent Developments and Anticipated Milestones - Build Upifitamab Rilsodotin (UpRi), a First-in-Class NaPi2b-Targeting ADC, into a Foundational Medicine in Ovarian Cancer...Nearing Completion of Dose Escalation in UPGRADE-A Trial: The dose escalation portion of UPGRADE-A, the company’s Phase 1/2 trial of UpRi in combination with carboplatin, is now nearly complete. The company expects to enter the dose expansion portion of UPGRADE-A in the first quarter of 2023 and plans to present data from the trial in the second half of 2023. Build a Pipeline of Highly Impactful Cancer Medicines....Readying for Initiation of XMT-2056 Phase 1 Trial...The company expects to initiate a multicenter Phase 1 open-label trial of XMT-2056 in previously treated patients with advanced/recurrent solid tumors expressing HER2, including breast, gastric, colorectal and non-small-cell lung cancers later in the fourth quarter of 2022."

P1/2 data • Trial status • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Gynecologic Cancers • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

Beyond Cytotoxic ADCs & Immunogenic Cell Death: Advancing ADCs Fully Into Immuno-oncology (ADC-USA 2022) - "SynopsisDesign and optimization of the Immunosynthen STING agonist ADC platformExtensive characterization of the pre-clinical profile of XMT-2056, a novel, Her-2 targeted Immunosynthen ADCTranslational Research demonstrating the mechanism of an Immnosynthen ADC and its ability to activate the STING pathway in tumor cells and tumor-resident immune cells to deliver a “1-2 punch”"

Immunogenic cell death • Oncology • HER-2