ZW191 / Zymeworks - LARVOL DELTA

Randomized dose optimization of ZW191 in heavily pretreated patients with platinum-resistant ovarian cancer (PROC) (ESMO 2026) - No abstract available

Clinical • Late-breaking abstract • Platinum resistant • Gynecologic Cancers • Oncology • Ovarian Cancer

Phase 1 first-in-human multicenter open-label study of ZW191, a folate receptor α (FRα)-targeting antibody-drug conjugate (ADC), in patients with advanced solid tumors: Part 1 dose-escalation results (AACR 2026) - P1 | "ZW191 demonstrated compelling efficacy regardless of FRα expression in a heavily pretreated population of patients with OC and EC, and a favorable safety profile. Dose levels of 6.4 and 9.6 mg/kg Q3W are being evaluated in the Part 2a dose optimization phase of the study."

ADC • Clinical • First-in-human • Metastases • P1 data • Endometrial Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • AVEN • FOLR1

Efficacy analysis of ZW191 by folate receptor α (FRα) expression level in a phase I study (ESMO-Gynae 2026) - "All patients were safety-evaluable; 28 (55%) reported grade ≥3 treatment-emergent adverse events, most commonly neutropenia (24%), anemia (20%), and thrombocytopenia (12%), across all doses. Conclusions ZW191 demonstrated compelling efficacy in patients with both positive and negative FRα expression levels, in a heavily pretreated population of OC and EC, along with a favorable safety profile."

Biomarker • Clinical • P1 data • Endometrial Cancer • Gynecologic Cancers • Ovarian Cancer • FOLR1

A Study of ZW191 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=145 | Recruiting | Sponsor: Zymeworks BC Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor

A Study of ZW191 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=145 | Not yet recruiting | Sponsor: Zymeworks BC Inc.

Metastases • New P1 trial • Oncology • Solid Tumor

Zymeworks Presents New Phase 1 Data for Folate Receptor Alpha-Targeting ADC ZW191 at ESMO Gynaecological Cancers Congress 2026 (GlobeNewswire) - "Among response-evaluable PROC patients, ZW191 demonstrated a cORR of 78.6% in patients with FRα-positive tumors and 47.4% in patients with FRα-negative tumors across all dose levels. Disease control rates were 100.0% and 89.5%, respectively. Confirmed ORR in the overall PROC population was 58.8% across all dose levels studied and 65.2% in dose range of 6.4-9.6 mg/kg....In endometrial cancer patients with FRα-negative tumors, ZW191 demonstrated a cORR of 40.0% and a disease control rate of 80.0% across all doses evaluated. Across both ovarian and endometrial cancer cohorts, responses were observed early and continued to deepen over time. Median duration of response was not reached at the time of data cutoff, and median progression-free survival was 7.6 months."

P1 data • Platinum resistant • Endometrial Cancer • Ovarian Cancer

Part 2a, the dose optimization portion of the Phase 1 study evaluating ZW191 in ~60 PROC patients randomized to either 6.4 mg/kg every three weeks or 9.6 mg/kg every three weeks, has completed enrollment (GlobeNewswire) - "Data from Part 2a will be presented at a future medical meeting and are expected to inform dose selection for potential future development."

Enrollment status • P1 data • Platinum resistant • Ovarian Cancer

ZW191: “ZW191 demonstrates a favorable clinical safety profile”; Endometrial and ovarian cancer (Zymeworks) - Corporate Presentation: “Anti-tumor activity of ZW191 in ovarian cancer (n=34)”

Endometrial Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer

ZW191 - a differentiated FRα-targeted topoisomerase I antibody drug conjugate active in combination with standard of care drugs (AACR 2026) - P1 | "ZW191 markedly improves on the FDA-approved FRα-targeted ADC mirvetuximab soravtansine in its efficacy in patient-derived xenograft tumors with both high and low level of FRα by virtue of its novel and highly effective FRα-targeted antibody and its novel ZD06519 TOPO1i payload...Here, we demonstrate ZW191's strong antitumor activity in a xenograft model of ovarian cancer when dosed in combination with each of the platinum-based drug carboplatin, the microtubule inhibitor paclitaxel, and the anti-angiogenic antibody bevacizumab...A clinical landscape analysis demonstrates that moderate potency ADC payloads facilitate higher dosing levels in the clinic. Together with encouraging early clinical data that highlight ZW191's single agent activity and differentiated safety profile, these data reinforce its potential to achieve meaningful efficacy gains through combination with other agents."

ADC • Combination therapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOLR1 • TOP1

ZWI-ZW191-101: A Study of ZW191 in Participants With Solid Tumors (clinicaltrials.gov) - P1 | N=145 | Active, not recruiting | Sponsor: Zymeworks BC Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor

ZW191, a FRα-targeted topoisomerase 1 inhibitor ADC with a differentiated antitumor efficacy and tolerability profile. (PubMed, Clin Cancer Res) - "ZW191 demonstrates favourable preclinical efficacy and tolerability. This differentiated profile is supported by initial clinical data, potentially positioning ZW191 to meaningfully improve responses and substantially widen the targetable patient population over standard of care."

Journal • Endometrial Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • FOLR1

Zymeworks Presents New Phase 1 Data for ZW191, a Folate Receptor Alpha-Targeting ADC at AACR Annual Meeting 2026 (GlobeNewswire) - "In platinum resistant ovarian cancer patients, ZW191 demonstrated a cORR of 56% across all dose levels, with tumor regression observed in 68% of patients and disease control achieved in 94%. Notably, ZW191 demonstrated compelling anti-tumor activity in the 6.4-9.6 mg/kg dose range regardless of FRα expression, with a cORR of 61% observed in ovarian and 57% in endometrial cancers, with disease control observed in 100% of patients....In endometrial cancer, ZW191 showed a cORR of 40% across all dose levels and 57% in the 6.4-9.6 mg/kg cohort, with disease control rates of 80% and 86%, respectively."

P1 data • Platinum resistant • Endometrial Cancer • Ovarian Cancer

New clinical data from Phase 1 trial of ZW191 to be presented in an oral presentation on April 21….at the American Association for Cancer Research (AACR) Annual Meeting 2026 (GlobeNewswire) - "Oral Presentation Details: Results from Part 1 dose escalation of ZWI-ZW191-101 study: Phase 1 first-in-human multicenter open-label study of ZW191, a folate receptor α (FRα)–targeting antibody-drug conjugate (ADC), in participants with advanced solid tumors; Abstract: CT306."

First-in-human • P1 data • Solid Tumor

ZW191 - a differentiated FRα-targeted topoisomerase I antibody drug conjugate active in combination with standard of care drugs (GlobeNewswire) - "Zymeworks presents new preclinical data at AACR 2026....Favorable tolerability profile, attributed to moderate potency TOPO1i payload and moderate stability linker, potentially achieves higher ADC dosing, better tolerability and improved combination potential with standard of care chemotherapeutics. Nonclinical in vitro and in vivo studies support the efficacious combination of ZW191 with standard of care therapies across multiple modes of action."

Preclinical • Solid Tumor

Design and development of biparatopic antibody-drug conjugates against protein tyrosine kinase 7 (AACR 2025) - P1 | "ADCs were produced by conjugating the top biparatopic and monoparatopic antibodies to ZD06519, a topoisomerase 1 inhibitor payload used in ZW191, an ADC targeting FRα under evaluation in a phase 1 clinical trial (NCT06555744). Across multiple cancer cell lines with varying PTK7 expression we compared a lead monoparatopic antibody and cofetuzumab with the top biparatopic antibody which demonstrated greater cell surface decoration and better internalization. At clinically relevant doses, the biparatopic ZD06519 ADC was more efficacious than cofetuzumab pelidotin in triple negative breast cancer and lung cancer cell line derived xenograft models. Additional studies of the PTK7 biparatopic ADC in patient-derived xenograft models and a non-human primate tolerability study are planned."

ADC • Breast Cancer • Cervical Cancer • Colorectal Cancer • Esophageal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • FOLR1 • PTK7

ZW191 - a FRα-targeting antibody drug conjugate with strong preclinical activity across multiple FRα-expressing indications (AACR 2024) - "The antibody component of ZW191 features a favorable binding profile with strong binding to FRα, and drives superior tumor spheroid penetration, cellular internalization, and payload delivery compared to FRα targeted antibodies used in multiple other ADCs. ZW191 demonstrates potent activity in FRα expressing cell cultures and effective bystander activity. In a panel of PDX models representing a range of FRα expression, ZW191 demonstrates compelling anti-tumor activity across ovarian and endometrial cancers, NSCLC and TNBC."

ADC • Preclinical • Endometrial Cancer • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • FOLR1

Zymeworks Inc…announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ZW191, an antibody-drug conjugate (ADC) targeting folate receptor-α (FRα), for the treatment of patients with advanced or metastatic platinum-resistant ovarian cancer (PROC). (GlobeNewswire) - "Ongoing Phase 1 clinical trial of ZW191 enrolling patients with advanced solid tumors to evaluate safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity."

Fast track • Platinum resistant • Trial status • Ovarian Cancer

The Company anticipates the following clinical development milestones from its R&D pipeline (GlobeNewswire) - "(i) The global Phase 1 clinical trial investigating ZW191 in solid tumors is ongoing with dose optimization of ZW191 in ovarian cancer. Additional data from the Phase 1 trial is anticipated to be presented at a major medical meeting in 2026; (ii) The global Phase 1 clinical trial investigating ZW251 in solid tumors is actively recruiting. The Company presented a Trial-in-Progress poster for ZW251, at ASCO Gastrointestinal Cancers Symposium (ASCO GI) on January 9, 2026; (iii) INDs for multispecific programs, ZW209...remain on track for submission in 2026."

IND • P1 data • Trial status • Ovarian Cancer

ZW191: “ZW191 has been safely administered during dose escalation up to 11.2 mg/kg, with the majority of participants still on treatment”; Solid tumor (Zymeworks) - Initial Results from the Phase 1 Trial of ZW191, an Antibody-Drug Conjugate Targeting Folate Receptor-⍺: “ORRs (uPR + cPR) between 6.4 mg/kg to 9.6 mg/kg were: 53% (overall) and 64% (GYN cancers)”

P1 data • Endometrial Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

Clinical Highlights: ZW191… (GlobeNewswire) - "Dose optimization to further evaluate safety and efficacy at 6.4 mg/kg and 9.6 mg/kg in ovarian cancer is expected to initiate in 4Q-2025."

Trial status • Ovarian Cancer

Preliminary results from a phase 1 first-in-human multicenter open-label study of ZW191, a folate receptor α–targeting antibody-drug conjugate, in patients with advanced solid tumors (AACR-NCI-EORTC 2025) - P1 | "ZW191 has been safely administered during dose escalation up to 9.6 mg/kg and has demonstrated preliminary efficacy across multiple dose levels, starting at 3.2mg/kg Q3W. Part 1 dose escalation is ongoing."

Clinical • First-in-human • Late-breaking abstract • Metastases • P1 data • Endometrial Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOLR1

Zymeworks Presents Initial Clinical Data from the Phase 1 trial of ZW191, an Antibody-Drug Conjugate Targeting Folate Receptor-⍺ at AACR-NCI-EORTC Conference (GlobeNewswire) - "Preliminary efficacy data, combined with a tolerable safety profile, reinforce the potential of ZW191 in patients with advanced solid tumors, including ovarian, endometrial, and non-small cell lung cancer. 64% overall response rate in gynecological cancers at doses ≥6.4mg/kg. Responses observed at all doses evaluated at 3.2mg/kg....Dose optimization of ZW191 in ovarian cancer to initiate in 4Q-2025."

P1 data • Trial status • Endometrial Cancer • Non Small Cell Lung Cancer • Ovarian Cancer

A Phase 1 study for ZW191 is actively recruiting and ZW251 is expected to enter clinical trials in 2025. (GlobeNewswire)

Trial status • Hepatocellular Cancer • Solid Tumor

Zymeworks to Present Clinical Data from the Phase 1 trial of ZW191, an Antibody-Drug Conjugate Targeting Folate Receptor-⍺, at AACR-NCI-EORTC International Conference (GlobeNewswire) - "Preliminary data presented at the AACR-NCI-EORTC conference will provide insights into the potential of ZW191 in patients with advanced solid tumors, including ovarian cancer, endometrial cancer, and non-small cell lung cancer."

P1 data • Endometrial Cancer • Non Small Cell Lung Cancer • Ovarian Cancer

Zymeworks Announces Decision to Discontinue Clinical Development of ZW171, a Mesothelin-directed T cell Engager (The Manila Times) - "The decision to discontinue clinical development of ZW171 was based on completion of the planned cohorts of the dose escalation portion of the Phase 1 trial of ZW171 in patients with ovarian cancer and non-small cell lung cancer....'We continue to advance our broader product pipeline, including the ongoing Phase 1 trial of ZW191 and the initiation of a Phase 1 study for ZW251 expected in 2025. We are also preparing an IND filing for ZW209, our DLL3-directed trispecific T cell engager, planned in the first half of 2026'."

Discontinued • IND • New P1 trial • Non Small Cell Lung Cancer • Ovarian Cancer