Jiangsu Hengrui’s Nectin-4 ADC gains China breakthrough status for cervical cancer

Jiangsu Hengrui Pharmaceuticals Co., Ltd. (HKEX: 600276), headquartered in Jiangsu province, China, announced that SHR-A2102, a Nectin-4–targeting antibody-drug conjugate (ADC) with a topoisomerase I inhibitor (TOP1i) payload, has been added to the Breakthrough Therapy Designation (BTD) list by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for the treatment of recurrent or metastatic cervical cancer following failure of platinum-based chemotherapy and PD-(L)1 inhibitor therapy. The drug is developed by Shanghai Hengrui Pharmaceuticals Co., Ltd., a subsidiary of the parent group. This is the second CDE breakthrough therapy designation for SHR-A2102; the first was granted in December 2024 for locally advanced or metastatic urothelial carcinoma in the same post-platinum, post-PD-(L)1 setting.

China’s BTD program, established under NMPA Announcement No. 82 of 2020, entitles the sponsor to prioritized CDE resource allocation, more frequent regulatory interaction, and active development guidance — mechanisms that can compress the path to a marketing application without constituting approval.

The cervical cancer population targeted by the designation faces limited options. Chinese Society of Clinical Oncology guidelines recommend single-agent chemotherapy after platinum and PD-(L)1 failure, a line of therapy that yields an overall response rate (ORR) of less than 10%, median progression-free survival (PFS) of approximately three months, and median overall survival (OS) of 8.5 to 9.5 months, according to data cited in the company’s filing.

No drug-specific cervical cancer efficacy dataset for SHR-A2102 was disclosed in the NMPA announcement. The most recent public efficacy data for the molecule come from a Phase I study (NCT05701709) presented at ASCO 2025, which enrolled 304 efficacy-evaluable patients with advanced solid tumors across multiple histologies. Across that population, SHR-A2102 produced an ORR of 35.2% (95% CI: 29.8–40.9%) and a disease control rate of 84.2%. In the urothelial carcinoma expansion cohort (n=73), ORR reached 38.3% overall and 50.0% at the 8 mg/kg dose. An earlier readout presented at ESMO 2024 (Annals of Oncology, DOI: 10.1016/j.annonc.2024.08.715) reported, among Nectin-4–positive patients, a cervical cancer ORR of 50%, rising to 75% in immunohistochemistry (IHC) 3+ tumors and 40% in IHC 2+ tumors, based on 38 evaluable patients with a data cutoff of April 9, 2024. These figures are from prior disclosures, not the current announcement.

The program has since advanced to Phase III testing in the designated cervical cancer population. A randomized, open-label, controlled Phase III study (NCT07418749) comparing SHR-A2102 against investigator’s choice chemotherapy in patients with platinum-based chemotherapy and PD-(L)1 inhibitor treatment-failed recurrent or metastatic cervical cancer is in progress, with a second Phase III record also indexed for the same indication. SHR-A2102 has also entered trials in urothelial carcinoma, bladder cancer, esophageal cancer, lung cancer, head and neck cancer, and breast cancer. Cumulative R&D investment in the asset reached approximately RMB 387.7 million as of the announcement date, on an unaudited basis.

Research context

The only globally approved Nectin-4–targeted ADC to date is enfortumab vedotin (Padcev; Astellas/Pfizer), which carries a monomethyl auristatin E (MMAE) payload — a microtubule-disrupting agent — rather than a TOP1i. According to EvaluatePharma data cited in the Hengrui filing, enfortumab vedotin generated approximately USD 2.473 billion in global sales in 2025. SHR-A2102 uses a TOP1i payload instead of MMAE, a distinction that may carry implications for tolerability profile and activity in tumors with prior MMAE exposure, though no head-to-head or crossover data are available in the public record.

Within the cervical cancer ADC space, 9MW2821, another Nectin-4 ADC in development, reported an ORR of 35.8%, disease control rate of 81.1%, median PFS of 3.9 months, median duration of response of 7.2 months, and a 12-month OS rate of 74.6% in 53 evaluable cervical cancer patients in 2024 data, with an ORR of 43.6% in Nectin-4 IHC 3+ tumors, according to a public disclosure. These figures provide class-level context for Nectin-4 targeting in cervical cancer but are not direct evidence for SHR-A2102’s performance. An active Phase II trial (NCT06654440) of SHR-A2102 in advanced gynecological malignancies is also currently recruiting.

The cervical cancer second-line and beyond setting has seen limited regulatory progress in China. First-line recurrent or metastatic disease is now addressed by pembrolizumab- and tislelizumab-based regimens in combination with platinum chemotherapy, but no targeted agent has been approved specifically for the post-platinum, post-checkpoint inhibitor population. The BTD designation positions SHR-A2102 as a candidate for potential drug approval in China in this setting, subject to Phase III outcomes that have not yet been reported.