upifitamab rilsodotin (XMT-1536)

P1, N=62, Completed, Mersana Therapeutics

P1, N=142, Completed, Mersana Therapeutics

P1/2, N=523, Active, not recruiting, Mersana Therapeutics | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2

P3, N=20, Terminated, Mersana Therapeutics | N=350 --> 20 | Trial completion date: Mar 2025 --> Sep 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Sep 2024 --> Sep 2023; Study Terminated by Sponsor

P1, N=31, Terminated, Mersana Therapeutics | N=48 --> 31 | Trial completion date: Mar 2025 --> Oct 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Nov 2024 --> Oct 2023; Study Terminated by Sponsor

P1, N=48, Active, not recruiting, Mersana Therapeutics | Recruiting --> Active, not recruiting

P3, N=350, Active, not recruiting, Mersana Therapeutics | Recruiting --> Active, not recruiting

In ovarian cancer, mirvetuximab soravtansine, an ADC targeting alpha-folate receptor (FRα), received US Food and Drug Administration (FDA) accelerated approval in November 2022 after data from the single-arm phase III SORAYA trial. A second ADC targeting FRα, STRO-002, received FDA fast track designation in August 2021. Multiple studies with upifitamab rilsodotin, an ADC comprising a NaPi2B-binding antibody, are underway. In cervical cancer, tisotumab vedotin, an ADC-targeting tissue factor, received FDA accelerated approval in September 2021 after the phase II innovaTV 204 trial...Trastuzumab-deruxtecan (T-DXd), an ADC targeting human epidermal growth factor receptor 2 (HER2), is currently approved for HER2-positive and HER2-low breast cancer and shows promise in endometrial cancer. Like all anticancer treatments, the decision for a patient to undergo therapy with an ADC is a personal choice that balances the potential benefits with the side effects and requires thorough and compassionate support of their physician and care team and shared decision making.

Patients who received bevacizumab in combination with their most recent platinum containing regimen are excluded...NCT05329545. Clinical trial information: NCT05329545.

NCT04907968. Clinical trial information: NCT04907968.

Background: Biomarker driven therapies are increasingly being used for gynecologic cancers, with mirvetuximab soravtansine, a Folate Receptor alpha (FRa) targeting antibody drug conjugate (ADC) being a recent FDA approved agent for patients with FRa positive PROC... Based on this analysis of a limited sample size, there does not appear to be an association between FRa and NaPi2b expression, with the majority of NaPi2b positive samples not being FRa positive. Additionally, general NaPi2b prevalence and the correlation of expression between RNA and IHC suggest that NaPi2b may be a rational biomarker to integrate in RNA tumor panel testing. This research underscores the importance of early, comprehensive testing of all relevant biomarkers to guide therapy selection, and suggests that additional research is needed to evaluate the potential association between FRa and NaPi2b expression via IHC.

P1, N=48, Recruiting, Mersana Therapeutics | Phase classification: P1/2 --> P1 | Trial completion date: Jul 2024 --> Mar 2025 | Trial primary completion date: Nov 2023 --> Nov 2024

P1b/2, N=444, Recruiting, Mersana Therapeutics | Trial completion date: Dec 2023 --> Dec 2024

Patients who received bevacizumab in combination with their last platinum containing regimen are excluded... N/A - trial in progress

UPGRADE-A is the first cohort evaluating UpRi in combination with carboplatin in patients with PSOC who have received 1-2 prior lines of therapy. trialinprogress

Patients who received bevacizumab in combination with their last platinum containing regimen are excluded. TrialinProgress

UpRi is being evaluated in clinical trials, requiring either fresh or archival tissue for NaPi2b expression assessment. The high expression concordance rate seen suggests that NaPi2b remains consistent throughout chemotherapy treatment, supporting use of archival tissue for analysis.

Antigen presentation genes showed decreased expression in fresh samples, suggesting tumors may evade immune surveillance during disease progression. Clinical trial information: NCT03319628.

P3, N=350, Recruiting, Mersana Therapeutics | Not yet recruiting --> Recruiting

P3, N=350, Not yet recruiting, Mersana Therapeutics

No abstract available

Learning Objective: Determine the optimized UpRi dose to improve long-term tolerability and the therapeutic index

No abstract available

The NaPi2b (67) assay system demonstrates a broad range of reproducible staining in OC. Current studies indicate that a ≥75% TPS cut-off could be used in a clinical setting for patient selection and identifies a similar population to the previously used H-score. This proposed CDx assay is currently being used in the UPLIFT Study Cohort of UpRi in OC (NCT03319628).

The 2 patients achieving CR had previously been treated with bevacizumab and PARPi (Richardson et al, ASCO 2021, TPS5607). Patients will be enrolled globally. ( NCT03319628 ).

P1b/2, N=444, Recruiting, Mersana Therapeutics | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Jul 2022 --> Apr 2023

The sodium-dependent phosphate transporter NaPi2b encoded by SLC34A2 gene is expressed in 80-90% of epithelial ovarian cancers and used as a target for therapeutic antibodies XMT-1536, and XMT-1592, which are derived from MX35 antibodies and used in clinical trials for the treatment of ovarian and lung cancers. In this work, we demonstrated that the expression of the human NaPi2b (hNaPi2b) transporter is downregulated in the tumors of patients receiving neoadjuvant therapy and during the development of disease. The data suggest that the level of expression of the SLC34A2 gene can serve as a potential marker for the monitoring and predicting responses to neoadjuvant and targeted therapy in patients with ovarian cancer.

P1/2, N=422, Ongoing, Mersana Therapeutics, Inc.

P1/2, N=54, Recruiting, Mersana Therapeutics | Not yet recruiting --> Recruiting

P1/2, N=54, Not yet recruiting, Mersana Therapeutics

Observation of preliminary antitumor activity was reported in the ovarian cancer expansion cohort, including in patients previously treated with bevacizumab and PARPi (Tolcher et al, ASCO 2019; Richardson et al, ASCO 2019; Hamilton et al, ESMO 2020) . This study is being conducted in collaboration with ENGOT and GOG . Patients will be enrolled globally.

Systemic free AF-HPA and AF concentrations were observed to be low in all animal species. Finally, we describe a unique immunohistochemical reagent, generated from a chimeric construct of the therapeutic antibody, that was used to derive a target expression and efficacy relationship in a series of ovarian primary xenograft cancer models.

P1b/2, N=420, Recruiting, Mersana Therapeutics | Phase classification: P1b --> P1b/2 | N=120 --> 420 | Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: May 2021 --> Jul 2022

P1b, N=120, Recruiting, Mersana Therapeutics | Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Jul 2020 --> May 2021

Results As of 01-May-2020, 27 pts with ovarian cancer have enrolled: median age was 70 years (range 55 to 85); median prior lines of therapy was 3 (range 1 to 5); >50% had received prior bevacizumab and/or a PARP inhibitor. Funding: Mersana Therapeutics, Inc. Clinical trial identification: NCT03319628.

Overall, XMT-1536 treatment demonstrated clinical activity in high grade serous ovarian cancer and NSCLC adenocarcinoma and was generally well-tolerated with no new safety signal trends identified in the EXP. Clinical efficacy and the relevance of NaPi2b expression for treatment with XMT-1536 will be presented. Research Funding: Mersana Therapeutics