FDA Fast Track for TUB-040: ADC Shows Promise in Treating Ovarian Cancer

Ovarian cancer: © Dr_Microbe - stock.adobe.com

• The FDA has granted a fast track designation to TUB-040 for the treatment of platinum-resistant ovarian cancer.
• TUB-040 is a next-generation NaPi2b-targeting exatecan antibody-drug conjugate (ADC).
• The agent is currently being evaluated in the multicenter phase 1/2a NAPISTAR 1-01 study (NCT06303505).

The ADC TUB-040 has been given FDA fast track designation for the treatment of platinum-resistant ovarian cancer. This designation aims to facilitate the development and expedite review of agents that fill unmet medical needs.¹

"Almost all patients with ovarian cancer who are not cured by initial therapy will develop resistance to platinum-based therapy over time. Once platinum-resistant, therapeutic options for these patients are poor with highly unsatisfactory outcomes. The FDA’s fast track designation of TUB-040 is an important step in the development of TUB-040 to provide these [patients] with urgently needed new therapeutic options," said Günter Fingerle-Rowson, MD, PhD, chief medical officer of Tubulis, in a press release. "The FDA decision brings us one step closer to our goal of delivering the true value of ADCs to patients in need, and we are grateful for the agency’s support on this path to develop TUB-040 fast and efficiently.”

TUB-040 is a NaPi2b-targeting exatecan ADC that delivers a ctopoisomerase I inhibitor to the tumor cells that overexpress NaPi2b. The ADC showed promise in preclinical models, including those for ovarian cancer. The phase 1/2a NAPISTAR 1-01 study is investigating the agent in patients with platinum-resistant, high-grade ovarian cancer and relapsed/refractory non–small cell lung cancer (NSCLC) who have exhausted other treatment options.

About NAPISTAR 1-01

The phase 1/2a NAPISTAR 1-01 is a first-in human trial investigating TUB-040 in patients with platinum-resistant ovarian cancer or relapsed/refractory NSCLC. An estimated 100 patients have been enrolled across centers in the US, United Kingdom, Spain, Belgium, and Germany.^1,2

The study’s primary end point is maximum tolerated dose (MTD), and secondary end points include pharmacokinetics, determination of immunogenicity, and overall response rate.² Patients receive TUB-040 intravenously on day 1 of a 21-day cycle until disease progression or unacceptable toxicity. After the MTD is identified in the dose-escalation phase, the dose-optimization phase will compare 2 dose levels to identify which is best for patients.

Patients are eligible if they have disease that is not amenable to curative intent, exhausted the standard-of-care treatment, an ECOG performance status of 0 to 1, a life expectancy of at least 12 weeks, adequate organ function, and resolution of toxicities from prior therapy (excepting alopecia, skin discoloration, or peripheral neuropathy). Those who are pregnant or breastfeeding, have a hypersensitivity to exatecan, have disease refractory to topoisomerase I inhibitors, have spinal cord compression or central nervous system disease, or have active and uncontrolled impairment of certain bodily systems are not eligible for enrollment in the study.

The study began enrollment in May 2024 and has an estimated completion date of January 2027.

REFERENCES:

1. Tubulis receives FDA fast track designation for antibody-drug conjugate candidate TUB-040 in platinum-resistant ovarian cancer. News release. Tubulis. June 27, 2024. Accessed June 27, 2024. https://tinyurl.com/4vt4ur2r

2. FiH study to investigate safety, PK and efficacy of the NaPi2b ADC TUB-040 in patients with PROC or r/r adenocarcinoma NSCLC (NAPISTAR1-01). ClinicalTrials.gov. Updated May 28, 2024. Accessed June 27, 2024. https://clinicaltrials.gov/study/NCT06303505