- UPLIFT clinical trial did not meet its primary endpoint
- Company realigns focus and significantly reduces expenses to extend cash runway into 2026
CAMBRIDGE, MA, USA I July 27, 2023 I Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, today announced that the UPLIFT clinical trial of upifitamab rilsodotin (UpRi) did not meet its primary endpoint. UpRi is an ADC targeting the sodium-dependent phosphate transport protein NaPi2b and was developed utilizing the company’s Dolaflexin platform.
UPLIFT was a single-arm clinical trial that enrolled platinum-resistant ovarian cancer patients with one to four prior treatment regimens. The primary endpoint for UPLIFT was the investigator-assessed objective response rate (ORR) in the NaPi2b-positive population. NaPi2b-positive status was defined by a tumor proportion score (TPS) of ≥75%. Secondary endpoints for the trial included the investigator-assessed ORR among all patients in the trial, duration of response (DOR), and safety and tolerability. The trial also included an assessment of ORR and DOR by independent radiology review (IRR).
UPLIFT enrolled a total of 268 patients, 141 of whom were determined to be NaPi2b positive. The median prior lines of systemic therapy among all patients was three, with 31% of the population having received four prior lines of treatment. Additionally, 84% of patients received prior bevacizumab and 69% received prior PARP inhibitor treatment.
Top-line results from UPLIFT as of the May 31, 2023 data cutoff date are as follows:
NaPi2b-Positive Population (n=141)
| |
Investigator Assessment |
IRR Assessment |
| ORR, n (%) [95% confidence interval] |
22 (15.6%) [10.0%, 22.7%] |
23 (16.3%) [10.6%, 23.5%] |
| Partial Response, n (%) |
20 (14.2%) |
16 (11.3%) |
| Complete Response, n (%) |
2 (1.4%) |
7 (5.0%) |
| Median DOR, months |
7.4 |
Not Reached |
Total Population (n=268)
| |
Investigator Assessment |
IRR Assessment |
| ORR, n (%) |
35 (13.1%) |
35 (13.1%) |
| Partial Response, n (%) |
32 (11.9%) |
24 (9.0%) |
| Complete Response, n (%) |
3 (1.1%) |
11 (4.1%) |
| Median DOR, months |
7.4 |
10.7 |
Safety and tolerability data in UPLIFT were generally consistent with prior disclosures. Following the completion of its analyses, the company plans to share detailed efficacy and safety data with the medical and scientific community in an appropriate forum.
“We are deeply disappointed that UPLIFT’s efficacy failed to replicate previous data from approximately 100 patients in the dose expansion portion of our Phase 1b clinical trial,” said Dr. Arvin Yang, Senior Vice President and Chief Medical Officer of Mersana Therapeutics. “While the duration of response was longer than that from the dose expansion portion of UpRi’s Phase 1b clinical trial, the lower bound of the confidence interval for the primary endpoint did not meet our goal of excluding a 12% ORR seen with standard-of-care single-agent chemotherapy. We are in the process of conducting an in-depth analysis of various factors to better understand the results as well as the characteristics of patients who responded to UpRi therapy, particularly those whose responses were deep and durable. We extend our deepest gratitude to all of the patients, family members, caregivers and investigators who contributed to UPLIFT.”
Strategic Reprioritization and Financial Update
“As an organization driven by a mission to discover and develop potentially life-changing ADCs for patients fighting cancer, UPLIFT’s outcome is clearly disappointing and requires us to reprioritize our areas of focus,” said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. “In recent years, Mersana has advanced new product candidates and developed new partnerships utilizing its next-generation ADC platforms, Dolasynthen and Immunosynthen. These will be our primary focus moving forward. We plan to complete the dose escalation portion of our Phase 1 clinical trial of XMT-1660 in 2023 and initiate the dose expansion portion of the trial in 2024. Our team continues working diligently to address the clinical hold on the Phase 1 clinical trial of XMT-2056. Additionally, we intend to strongly support Mersana’s collaborators as they leverage our next-generation ADC platforms and advance their product candidates.”
“We also are taking decisive action to extend our cash runway and ensure we have the resources to evaluate the clinical potential of our next-generation ADC product candidates,” Ms. Protopapas continued. “Unfortunately, this necessitates reducing our workforce by approximately 50%. A very talented group of employees who helped to build Mersana will be departing as a result of this strategic reprioritization. We are grateful for their many contributions and intend to provide strong support through their transition.”
Mersana’s restructuring plan includes a wind-down of UpRi-related development activities, including its UP-NEXT and UPGRADE-A clinical trials and the company’s regulatory and commercial readiness efforts. If analyses of data enable the identification of a path forward for UpRi, the company will consider strategic alternatives for the asset, including partnering.
Mersana estimates that its balance of cash, cash equivalents and marketable securities as of June 30, 2023 was $286.6 million. This figure is preliminary and is subject to completion of the company’s financial closing procedures. The company expects to report its cash, cash equivalents and marketable securities, as well as other information necessary for a complete understanding of its financial position, in its Quarterly Report on Form 10-Q for the quarter ended June 30, 2023. The company expects that its available funds will be sufficient to support its current operating plan commitments into 2026.
About Mersana Therapeutics
Mersana Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel antibody-drug conjugates (ADCs) and driven by the knowledge that patients are waiting for new treatment options. The company has developed proprietary cytotoxic (Dolasynthen) and immunostimulatory (Immunosynthen) ADC platforms that are generating a pipeline of wholly-owned and partnered product candidates with the potential to treat a range of cancers. Its pipeline includes XMT-1660, a Dolasynthen ADC targeting B7-H4, and XMT-2056, an Immunosynthen ADC targeting a novel epitope of human epidermal growth factor receptor 2 (HER2). Mersana routinely posts information that may be useful to investors on the “Investors & Media” section of its website at www.mersana.com.
SOURCE: Mersana Therapeutics
Post Views: 252
- UPLIFT clinical trial did not meet its primary endpoint
- Company realigns focus and significantly reduces expenses to extend cash runway into 2026
CAMBRIDGE, MA, USA I July 27, 2023 I Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, today announced that the UPLIFT clinical trial of upifitamab rilsodotin (UpRi) did not meet its primary endpoint. UpRi is an ADC targeting the sodium-dependent phosphate transport protein NaPi2b and was developed utilizing the company’s Dolaflexin platform.
UPLIFT was a single-arm clinical trial that enrolled platinum-resistant ovarian cancer patients with one to four prior treatment regimens. The primary endpoint for UPLIFT was the investigator-assessed objective response rate (ORR) in the NaPi2b-positive population. NaPi2b-positive status was defined by a tumor proportion score (TPS) of ≥75%. Secondary endpoints for the trial included the investigator-assessed ORR among all patients in the trial, duration of response (DOR), and safety and tolerability. The trial also included an assessment of ORR and DOR by independent radiology review (IRR).
UPLIFT enrolled a total of 268 patients, 141 of whom were determined to be NaPi2b positive. The median prior lines of systemic therapy among all patients was three, with 31% of the population having received four prior lines of treatment. Additionally, 84% of patients received prior bevacizumab and 69% received prior PARP inhibitor treatment.
Top-line results from UPLIFT as of the May 31, 2023 data cutoff date are as follows:
NaPi2b-Positive Population (n=141)
| |
Investigator Assessment |
IRR Assessment |
| ORR, n (%) [95% confidence interval] |
22 (15.6%) [10.0%, 22.7%] |
23 (16.3%) [10.6%, 23.5%] |
| Partial Response, n (%) |
20 (14.2%) |
16 (11.3%) |
| Complete Response, n (%) |
2 (1.4%) |
7 (5.0%) |
| Median DOR, months |
7.4 |
Not Reached |
Total Population (n=268)
| |
Investigator Assessment |
IRR Assessment |
| ORR, n (%) |
35 (13.1%) |
35 (13.1%) |
| Partial Response, n (%) |
32 (11.9%) |
24 (9.0%) |
| Complete Response, n (%) |
3 (1.1%) |
11 (4.1%) |
| Median DOR, months |
7.4 |
10.7 |
Safety and tolerability data in UPLIFT were generally consistent with prior disclosures. Following the completion of its analyses, the company plans to share detailed efficacy and safety data with the medical and scientific community in an appropriate forum.
“We are deeply disappointed that UPLIFT’s efficacy failed to replicate previous data from approximately 100 patients in the dose expansion portion of our Phase 1b clinical trial,” said Dr. Arvin Yang, Senior Vice President and Chief Medical Officer of Mersana Therapeutics. “While the duration of response was longer than that from the dose expansion portion of UpRi’s Phase 1b clinical trial, the lower bound of the confidence interval for the primary endpoint did not meet our goal of excluding a 12% ORR seen with standard-of-care single-agent chemotherapy. We are in the process of conducting an in-depth analysis of various factors to better understand the results as well as the characteristics of patients who responded to UpRi therapy, particularly those whose responses were deep and durable. We extend our deepest gratitude to all of the patients, family members, caregivers and investigators who contributed to UPLIFT.”
Strategic Reprioritization and Financial Update
“As an organization driven by a mission to discover and develop potentially life-changing ADCs for patients fighting cancer, UPLIFT’s outcome is clearly disappointing and requires us to reprioritize our areas of focus,” said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. “In recent years, Mersana has advanced new product candidates and developed new partnerships utilizing its next-generation ADC platforms, Dolasynthen and Immunosynthen. These will be our primary focus moving forward. We plan to complete the dose escalation portion of our Phase 1 clinical trial of XMT-1660 in 2023 and initiate the dose expansion portion of the trial in 2024. Our team continues working diligently to address the clinical hold on the Phase 1 clinical trial of XMT-2056. Additionally, we intend to strongly support Mersana’s collaborators as they leverage our next-generation ADC platforms and advance their product candidates.”
“We also are taking decisive action to extend our cash runway and ensure we have the resources to evaluate the clinical potential of our next-generation ADC product candidates,” Ms. Protopapas continued. “Unfortunately, this necessitates reducing our workforce by approximately 50%. A very talented group of employees who helped to build Mersana will be departing as a result of this strategic reprioritization. We are grateful for their many contributions and intend to provide strong support through their transition.”
Mersana’s restructuring plan includes a wind-down of UpRi-related development activities, including its UP-NEXT and UPGRADE-A clinical trials and the company’s regulatory and commercial readiness efforts. If analyses of data enable the identification of a path forward for UpRi, the company will consider strategic alternatives for the asset, including partnering.
Mersana estimates that its balance of cash, cash equivalents and marketable securities as of June 30, 2023 was $286.6 million. This figure is preliminary and is subject to completion of the company’s financial closing procedures. The company expects to report its cash, cash equivalents and marketable securities, as well as other information necessary for a complete understanding of its financial position, in its Quarterly Report on Form 10-Q for the quarter ended June 30, 2023. The company expects that its available funds will be sufficient to support its current operating plan commitments into 2026.
About Mersana Therapeutics
Mersana Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel antibody-drug conjugates (ADCs) and driven by the knowledge that patients are waiting for new treatment options. The company has developed proprietary cytotoxic (Dolasynthen) and immunostimulatory (Immunosynthen) ADC platforms that are generating a pipeline of wholly-owned and partnered product candidates with the potential to treat a range of cancers. Its pipeline includes XMT-1660, a Dolasynthen ADC targeting B7-H4, and XMT-2056, an Immunosynthen ADC targeting a novel epitope of human epidermal growth factor receptor 2 (HER2). Mersana routinely posts information that may be useful to investors on the “Investors & Media” section of its website at www.mersana.com.
SOURCE: Mersana Therapeutics
Post Views: 252
