FDA Grants Fast Track Designation to TUB-040 for Ovarian Cancer

The FDA granted the antibody drug conjugate (ADC) TUB-040 a fast track designation for the treatment of patients with platinum-resistant high-grade ovarian cancer (PROC), demonstrating superior biophysical properties with durable responses. The designation, based on results observed in phase 1/2a NAPISTAR 1-01 (NCT06303505) study, will increase FDA interaction with TIB-040 for developmental support to expedite the treatment to regulatory review, bringing high-risk patients closer to additional therapeutic options.

The preclinical pharmacokinetic analysis demonstrated that TUB-040 efficiently targets tumors while minimizing off-site toxicities in surrounding organs, offering patients more promising, targeted therapy options. Image Credit: © Chinnapong - stock.adobe.com

According to the American Cancer Society, 19,680 women will receive an OC diagnosis in 2024, and 12,740 women will die from the disease. OC is the leading cause of cancer deaths among women diagnosed with gynecological cancers and is often diagnosed in later stages, due to its non-specific clinical symptoms and lack of preventative screening methods. Current standard of care for OC involves platinum-based chemotherapy; however these treatments lack selectively, have high systemic toxicity, and drug resistance, resulting in poorer outcomes for patients.^1,2

Approximately 20% of patients are platinum-resistant, meaning their disease relapsed during or within 6 months after completing treatment. PROC is associated with significantly poorer disease outcomes and often leaves patients with a median survival of 12 to 16 months, emphasizing the high unmet medical needs of this population. However, development of ADCs holds promising therapeutic potential for patients, especially in the platinum-resistant setting.³

ADCs molecules comprised of a monoclonal antibody directed at tumor-targeted antigens chemically linked to a highly potent cytotoxic agent, allowing them to target specific cancer antigens expressed only on cancer cells. Since 2022, the FDA has approved 13 ADC treatments for solid tumors, beginning with mirvetuximab soravtansine (MIRV) for OC, which demonstrated a considerably higher response rate in patients with PROC.⁴

TUB-040 is an ADC directed against Napi2b, a transmembrane protein that functions as a sodium-dependent phosphate transporter to moderate phosphate homeostasis. Prior studies suggest that Napi2b plays a role in tumorigeneses due to the dysregulation of phosphate homeostasis. TUB-040 consists of a IgG1 antobody targeting Napi2b connected to topoisomerase 1 inhibitor exatecan through a cleavable linker system based on P5 conjugation technology with homogenous DAR of 8.^3,5

NAPISTAR 1-01 is a multicentric, open-label trial evaluating the safety, tolerability, pharmacokinetics and preliminary efficacy of TUB-040 for patients with OC or non-small cell lung cancer. The study consists of 2 parts: dose escalation and dose optimization. During dose escalation, patients are to receive increasing doses of TUB-040 until tolerated dosage is observed. In dose optimization, at least 2 doses are compared with each other to determine the best dose for patients. TUB-040 is given intravenously every 3 weeks until disease progression or treatment termination due to adverse effects.⁶

The preclinical pharmacokinetic analysis demonstrated that TUB-040 efficiently targets tumors while minimizing off-site toxicities in surrounding organs, offering patients with PROC more promising targeted therapy options. Investigations into the safety and efficacy of TUB-040 are to continue in the NAPISTAR 1-01 study, which is projected to complete in January 2027.³

“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 women with urgently needed new therapeutic options,“ Günter Fingerle-Rowson, MD, PhD, chief medical officer of Tubulis, said in a press release. “The FDA decision brings us 1 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.”³

References

1. Key statistics for ovarian cancer. American Cancer Society. Accessed June 28, 2024. https://www.cancer.org/cancer/types/ovarian-cancer/about/key-statistics.html

2. Zhang C, Xu C, Gao X, Yao Q. Platinum-based drugs for cancer therapy and anti-tumor strategies. Theranostics. February 7, 2022. doi:10.7150/thno.69424

3. Tubilis receives FDA fast track designation for antibody-drug conjugate candidate TUB-040 in platinum-resistant ovarian cancer. Tubilis. June 27, 2024. Accessed June 28, 2024. https://tubulis.com/news/tubulis-receives-fda-fast-track-designation-for-antibody-drug-conjugate-candidate-tub-040-in-platinum-resistant-ovarian-cancer/

4. New developments in antibody-drug conjugates for the treatment of ovarian and urothelial carcinomas. ASCO Daily News. March 22, 2023. Accessed June 28, 2024. https://dailynews.ascopubs.org/do/new-developments-antibody-drug-conjugates-treatment-ovarian-and-urothelial-carcinomas

5. Banerjee S, Drapkin R, Richardson D, et al. Targeting NaPi2b in ovarian cancer. Cancer Treatment Reviews. November 14, 2022. doi:10.1016/j.ctrv.2022.102489

6. First-in-Human Study to Investigate Safety, Tolerability, Pharmacokinetics, and Efficacy of the NaPi2b ADC TUB-040 in Patients With Platinum-Resistant High-Grade Ovarian Cancer or Relapsed/Refractory Adenocarcinoma Non-Small Cell Lung Cancer (NAPISTAR 1-01). Tubulis. ClinicalTrials.gov. May 28, 2024. Accessed June 28, 2024.https://clinicaltrials.gov/ct2/show/NCT06303505.