SHR-A1904: CLDN18.2-Targeting Antibody-Drug Conjugate as Second-Line Monotherapy for Advanced Neuroendocrine Carcinoma
NCT07520357 is a Phase II single-arm trial evaluating SHR-A1904 โ Hengrui's CLDN18.2-targeting antibody-drug conjugate (ADC) โ as second-line or later monotherapy in patients with advanced neuroendocrine carcinoma (NEC) who have progressed after platinum-based chemotherapy. The trial is sponsored by Beijing GoBroad Hospital and led by Professor Ming Lu โ Chief Physician of the Department of Gastrointestinal Oncology at Peking University Cancer Hospital and Beijing GoBroad Hospital, and China's leading clinician-researcher in neuroendocrine neoplasm treatment. The trial is expected to open for enrollment in April 2026. CancerFax helps eligible patients prepare records and connect with the trial team in advance of opening.
About This Clinical Trial
Advanced neuroendocrine carcinoma (NEC) โ encompassing poorly differentiated, high-grade neuroendocrine malignancies (Ki-67 > 20%, grade 3) arising from the gastrointestinal tract, pancreas, lung, and other primary sites โ is a rare and aggressive cancer with one of the bleakest prognoses in oncology. First-line platinum-based chemotherapy (etoposide/cisplatin or carboplatin) achieves response rates of 40โ67% but durability is short, with median progression-free survival of 4โ8 months. At disease progression after first-line treatment, there is no established standard second-line therapy: FOLFIRI (irinotecan + 5-FU/leucovorin) is the best-supported option based on the PRODIGE 41-BEVANEC randomised Phase 2 trial, but median OS from second-line therapy is only ~6 months. This profound unmet need has made advanced NEC an urgent target for novel therapeutic investigation.
NCT07520357 is a prospective, single-centre, Phase 2 trial sponsored by Beijing GoBroad Hospital, led by Professor Ming Lu โ Chief Physician of Gastrointestinal Oncology at Peking University Cancer Hospital / Beijing GoBroad Hospital and China's most prominent clinician-researcher in neuroendocrine neoplasm treatment. The trial evaluates SHR-A1904 as monotherapy in second-line or later treatment of advanced NEC. SHR-A1904 is an antibody-drug conjugate (ADC) developed by Hengrui Medicine (Jiangsu Hengrui Pharmaceuticals Co. Ltd.) โ comprising a CLDN18.2-targeting IgG1 monoclonal antibody, a cleavable peptide-based linker, and a DNA topoisomerase I inhibitor (camptothecin-based) cytotoxic payload.
The scientific rationale for testing SHR-A1904 in NEC centres on Claudin 18.2 (CLDN18.2) โ a tight-junction protein highly expressed in gastric, pancreatic, and certain other gastrointestinal epithelial cancers, and increasingly identified as expressed in a subset of gastric and pancreatic neuroendocrine carcinomas. Published data confirm that CLDN18.2 is positive as a gastric-origin marker in neuroendocrine tumours, and a subset of gastric and pancreatic NECs have demonstrated CLDN18.2 expression. Professor Ming Lu has explicitly identified CLDN18.2-targeted therapy as a promising emerging approach for NEC treatment in his published clinical commentary. This trial is the first Phase 2 study of a CLDN18.2-targeted ADC specifically designed for advanced NEC โ a population that is not addressed by the currently approved CLDN18.2-targeted therapies (which focus on gastric and gastroesophageal junction adenocarcinoma).
SHR-A1904 itself has a compelling published profile: a Phase 1 trial published in Nature Medicine (Ruan et al., Nat Med 2025;31:3037โ3046) in 95 patients with CLDN18.2-positive advanced gastric/GEJ cancer demonstrated an ORR of 55.6% at 6 mg/kg with a disease control rate of 88.9% โ among the highest ORRs reported for any ADC in this disease space. The drug is now in Phase 3 development for gastric cancer. This NEC trial extends that validated platform to a new, desperately underserved indication.
Advanced NEC has median OS of approximately 6 months after first-line progression. There is no regulatory approval for any second-line agent. This trial brings a well-characterised ADC with published Phase 1 activity in related CLDN18.2-expressing cancers to a population with no approved options.
Trial at a Glance
Key registry details for NCT07520357. This trial is not yet recruiting โ planned start April 30, 2026. Patients should register early interest with CancerFax to be prepared when enrollment opens.
NCT07520357 is not yet accepting patients. Register early interest through CancerFax to be notified when enrollment opens and to have your records prepared in advance.
Treatment Being Studied
SHR-A1904 is administered as an intravenous infusion on a Q3W (every 3 weeks) schedule. After binding to CLDN18.2 expressed on NEC tumour cells, the ADC is internalised into the cell. The cleavable linker is then processed by intracellular proteases, releasing the topoisomerase I inhibitor payload, which induces irreparable DNA double-strand breaks and tumour cell death.
Because this is a Phase 2 single-arm study (rather than a dose-escalation Phase 1), patients receive the dose established from the Phase 1 programme in gastric/GEJ cancer. The trial is designed specifically to evaluate ORR โ the proportion of patients achieving confirmed tumour response โ as the primary endpoint, which is the standard efficacy measure for a Phase 2 single-arm cancer drug trial.
How the therapy works (in simple terms)
How it is given
Patients with histologically confirmed advanced NEC are assessed for eligibility. A tumour tissue sample (obtained within 2 years or freshly biopsied) must be available โ this will be used for exploratory biomarker analysis including CLDN18.2 expression, even though CLDN18.2 positivity is not required for eligibility. Prior treatment history is verified: patients must have progressed on at least one line of platinum-based chemotherapy; prior CLDN18.2-targeted therapy and prior topoisomerase I inhibitor ADC are exclusions.
Confirmatory imaging (CT or equivalent), complete blood count and organ function panel (within 14 days), cardiac ultrasound (LVEF โฅ 50% required), and coagulation tests are performed. At least one measurable lesion per RECIST v1.1 criteria must be present and must not have received prior local radiation therapy.
SHR-A1904 is administered as an IV infusion every 3 weeks (Q3W). The Phase 1-established dose (6.0 mg/kg or 8.0 mg/kg) will be used. Treatment continues until disease progression, unacceptable toxicity, patient withdrawal, or investigator decision to discontinue.
Tumour response is assessed by imaging per RECIST v1.1 criteria at regular intervals throughout treatment. The primary endpoint โ ORR โ is the proportion of patients achieving confirmed complete response (CR) or partial response (PR). Secondary endpoints (PFS, OS, DCR, DOR) are assessed throughout the approximately 2-year follow-up period.
Patients responding to or deriving benefit from treatment may continue SHR-A1904 infusions. Safety monitoring via adverse event recording (CTCAE v5.0) continues throughout. Primary completion is planned for February 2028; full study completion for February 2029.
Unlike most trials in this CancerFax series, NCT07520357 is a Phase 2 efficacy trial โ not a Phase 1 safety/dose-escalation study. Participants receive the drug at the dose established from Phase 1 experience and the primary question is whether the drug produces measurable tumour responses in advanced NEC. This makes it a direct test of efficacy โ and a more definitive trial for patients seeking information on likely benefit.
Who This Trial May Be For
The following profiles reflect the published eligibility criteria for NCT07520357. Only the trial investigators at Beijing GoBroad Hospital can confirm eligibility after reviewing full medical records. Prof. Ming Lu's team can be contacted via CancerFax.
Patients must have a tissue biopsy-confirmed diagnosis of advanced NEC. This includes poorly differentiated, high-grade neuroendocrine carcinomas (Ki-67 > 20%, WHO Grade 3) from any primary site โ but excludes Merkel cell carcinoma, neuroendocrine prostate cancer, and medullary thyroid carcinoma (explicit exclusions in the registry).
Patients must have progressed on previous standard therapy โ with at minimum documented progression after one line of platinum-based chemotherapy (etoposide/cisplatin, etoposide/carboplatin, or equivalent). This is the standard first-line approach for advanced NEC.
Patients who have previously received zolbetuximab (Vyloy), other anti-CLDN18.2 antibodies or ADCs, or any antibody-drug conjugate containing a topoisomerase I inhibitor payload are not eligible. This is a critical exclusion: patients who have received irinotecan or other topoisomerase I inhibitor small molecules (not ADCs) appear to remain eligible.
A tumour tissue sample is mandatory โ either from a biopsy performed within the last 2 years, or a freshly obtained sample. Archival formalin-fixed paraffin-embedded tissue is acceptable if within the time window. This sample will be used for exploratory CLDN18.2 and other biomarker analyses.
Good performance status (ECOG 0: fully active; or ECOG 1: restricted in strenuous activity but ambulatory and capable of self-care) is required. Life expectancy โฅ 12 weeks is required. This is somewhat less restrictive than ECOG 0โ1 trials requiring โฅ 3 month survival, as 12 weeks is approximately equivalent to 3 months.
Age range 18โ75 years. Adequate marrow function (ANC โฅ 1.5ร10โน/L, PLT โฅ 100ร10โน/L, Hb โฅ 90 g/L); liver function (ALT/AST โค 3ร ULN; โค 5ร ULN with liver metastases; TBIL โค 1.5ร ULN); renal function (Cr โค 1.5ร ULN or creatinine clearance โฅ 60 mL/min); coagulation (PT/APTT โค 1.5ร ULN); cardiac (LVEF โฅ 50%).
Eligibility Criteria
The following criteria are taken directly from the ClinicalTrials.gov registry for NCT07520357. Only Prof. Ming Lu's team at Beijing GoBroad Hospital can confirm eligibility after reviewing complete medical records.
check_circleInclusion Criteria โ May Be Eligible
- โWilling to participate; signed informed consent; good adherence; able to cooperate with follow-up
- โAge 18โ75 years, both genders
- โHistologically confirmed advanced neuroendocrine carcinoma
- โProgressed after previous standard therapy โ at minimum, progressed after first-line platinum-based chemotherapy
- โTumour tissue samples available โ within 2 years or freshly obtained
- โAt least one measurable lesion per RECIST v1.1 criteria (must not have received prior local therapy such as radiotherapy)
- โECOG performance status 0 or 1
- โLife expectancy โฅ 12 weeks
- โANC โฅ 1.5ร10โน/L; PLT โฅ 100ร10โน/L; Hb โฅ 90 g/L (no blood transfusion or growth factors within 14 days before test)
- โALT and AST โค 3ร ULN (โค 5.0ร ULN if liver metastases); TBIL โค 1.5ร ULN (Gilbert's syndrome: TBIL โค 3 mg/dL)
- โSerum creatinine โค 1.5ร ULN or creatinine clearance โฅ 60 mL/min (Cockcroft-Gault)
- โPT โค 1.5ร ULN; APTT โค 1.5ร ULN
- โCardiac LVEF โฅ 50% by echocardiography
- โFemale patients of childbearing age or male patients with childbearing-age female partners must use highly effective contraception during study and for 6 months after last dose
cancelExclusion Criteria โ May Not Be Eligible
- รPrevious receipt of claudin 18.2-targeted therapy
- รPrevious receipt of any drug containing a topoisomerase I inhibitor drug, including antibody-drug conjugates
- รMerkel cell carcinoma, neuroendocrine prostate cancer, or medullary thyroid carcinoma
- รUntreated brain metastasis, or with meningeal metastasis or spinal cord compression (treated, stable brain metastases โฅ 4 weeks on imaging, off systemic steroids > 2 weeks and asymptomatic: eligible)
- รSpinal cord compression not curable by surgery and/or radiotherapy
- รUncontrolled cancer-related pain
- รSymptomatic pleural effusion, pericardial effusion, or ascites requiring drainage or therapeutic drainage within 2 weeks before first dose
- รAnti-tumour therapy (chemotherapy etc.) within 3 weeks before first dose, or within 5 half-lives (whichever is shorter)
- รMajor organ surgery or major trauma within 4 weeks before first dose
- รOther malignant tumours within 3 years before first treatment (except: basal or squamous cell skin cancer, cervical carcinoma in situ, DCIS, and radically treated thyroid cancer)
- รActive interstitial lung disease, history of ILD, or history of non-infectious pneumonia (any grade)
- รUnexplained fever > 38.5ยฐC before first dose; or grade > 2 severe infection within 4 weeks before first dose
- รGastrointestinal perforation/fistula within 6 months; active GI bleeding within 3 months
- รArterial/venous thrombotic events requiring intervention within 6 months before first dose
- รUncontrolled hypertension (SBP โฅ 140 mmHg or DBP โฅ 90 mmHg); history of hypertensive crisis or hypertensive encephalopathy
- รRefractory nausea, vomiting, or chronic gastrointestinal diseases
- รActive autoimmune disease or history of organ transplantation; HIV-positive
- รActive hepatitis B or hepatitis C
- รLive or attenuated vaccine within 4 weeks before first dose
- รUnresolved adverse reactions from prior anti-tumour therapy (> CTCAE Grade 1)
- รHistory of severe allergic reaction to other monoclonal antibodies or to any component of SHR-A1904
- รOther factors judged by investigator to affect study results (alcohol/drug abuse, serious comorbidities, severe lab abnormalities, social/family factors)
(1) Prior claudin 18.2-targeted therapy; (2) Prior any topoisomerase I inhibitor ADC; (3) Merkel cell carcinoma, neuroendocrine prostate cancer, and medullary thyroid carcinoma are excluded histological subtypes. Patients with these histories or diagnoses are not eligible.
Medical Records and Tests Needed for Review
To begin the eligibility review, CancerFax will need the following documents. The mandatory tumour tissue sample requirement and the exclusion of prior CLDN18.2 and topo-I ADC therapy are the most important items to confirm before submitting.
Potential Benefits
These reflect the scientific rationale and the published evidence base for SHR-A1904 in related tumour types. Clinical outcomes in advanced NEC specifically are unknown โ this trial is designed to generate that data.
SHR-A1904's Phase 1 trial (published Nature Medicine, July 2025) demonstrated an ORR of 55.6% and DCR of 88.9% in CLDN18.2-positive advanced gastric/GEJ cancer at 6 mg/kg. These are among the highest response rates reported for any ADC in this cancer type. While NEC is biologically distinct, the shared CLDN18.2 biology in gastric/pancreatic NECs provides a rational foundation for anticipating activity.
Beyond the topoisomerase I inhibitor payload, SHR-A1904's IgG1 antibody component can trigger ADCC (antibody-dependent cellular cytotoxicity) and CDC (complement-dependent cytotoxicity) โ direct immune-mediated tumour killing that is distinct from and complementary to the payload mechanism. This dual-mechanism property of IgG1 ADCs may contribute to more durable responses compared to chemotherapy alone.
SHR-A1904 is administered as a standard intravenous infusion on a Q3W outpatient-compatible schedule. Unlike some experimental therapies requiring surgical procedures, cell collection, or intensive inpatient stays, this ADC can be administered in a standard oncology infusion suite.
Most trials in the CancerFax series are Phase 1 safety studies where efficacy is exploratory. NCT07520357 is a Phase 2 efficacy trial โ designed specifically to generate definitive ORR data. A positive result would provide the evidence base for further development and potential future approval of SHR-A1904 in NEC.
Professor Ming Lu is Chief Physician of Gastrointestinal Oncology at both Peking University Cancer Hospital and Beijing GoBroad Hospital โ with a published NEN research programme and a GoBroad Healthcare Group profile as the leading NEN clinician-researcher in China. The trial benefits from his deep expertise in NEC treatment and his direct familiarity with CLDN18.2 as an NEC target.
All participants contribute tumour tissue samples for exploratory biomarker analysis, including CLDN18.2 expression profiling. This biomarker collection may identify which NEC patients derive the most benefit from CLDN18.2-targeted ADC therapy โ informing future precision treatment algorithms in NEC.
Advanced NEC after platinum failure has no approved second-line treatment globally. This trial brings a drug with 55.6% ORR in CLDN18.2-positive gastric cancer to a new, underserved population โ guided by a leading NEN specialist who has explicitly identified this target as relevant to NEC biology.
Risks and Side Effects
SHR-A1904's safety profile in advanced NEC is not yet characterised โ this Phase 2 trial will generate the first formal NEC-specific safety data. The risk profile below draws on the published Phase 1 experience in gastric/GEJ cancer as the most directly relevant available data.
In the Phase 1 gastric/GEJ trial, dose-limiting toxicities at 4.8 mg/kg included grade 3 febrile neutropenia. Neutropenia, anaemia, and thrombocytopenia are class-effect risks for topoisomerase I inhibitor ADCs. Regular blood count monitoring throughout treatment is standard practice.
CLDN18.2 is physiologically expressed in normal gastric epithelial tight junctions. Anti-CLDN18.2 therapy can cause gastric mucosal injury โ one patient at 6.0 mg/kg in the Phase 1 trial experienced a dose-limiting grade 3 gastric mucosal lesion. Nausea, vomiting, diarrhoea, and elevated transaminases were also reported. The trial appropriately excludes patients with refractory nausea/vomiting and active GI bleeding.
Interstitial lung disease and pneumonitis are known class-effect risks for topoisomerase I inhibitor ADCs โ prominently observed with trastuzumab deruxtecan (Enhertu). The trial explicitly excludes patients with a history of ILD or non-infectious pneumonitis of any grade. Active monitoring for pulmonary symptoms throughout treatment is standard. Early recognition and management of ILD is critical.
One DLT at 4.8 mg/kg in the Phase 1 trial was grade 3 elevated blood bilirubin. Transaminase elevations were also observed across the dose escalation cohorts. Regular liver function monitoring (ALT, AST, bilirubin) is required per protocol.
As with all monoclonal antibody infusions, hypersensitivity and infusion-related reactions (fever, chills, urticaria, bronchospasm) are possible. Patients with a history of severe allergic reactions to monoclonal antibodies are excluded. Standard pre-medication protocols are used.
Baseline LVEF โฅ 50% is required, and cardiac monitoring is included in the protocol. While cardiotoxicity is less prominent with CLDN18.2 ADCs than with HER2-targeted ADCs, the inclusion of cardiac monitoring reflects standard Phase 2 oncology practice and the general principle of vigilance for drug-related cardiac effects.
The adverse events below reflect SHR-A1904's safety profile in CLDN18.2-positive advanced gastric/GEJ cancer patients (Nature Medicine, 2025). NEC patients may have a different risk profile depending on disease burden, prior treatment history, and tumour biology. All participants receive close monitoring by Prof. Ming Lu's team.
Costs, Trial Coverage, and Patient Expenses
As an industry-sponsored Phase 2 trial funded by Jiangsu Hengrui Pharmaceuticals and Beijing GoBroad Hospital, the investigational drug SHR-A1904 and protocol-required testing are expected to be provided at no direct cost to participants. Confirm specifics with the trial team.
In industry-sponsored Phase 2 trials, the investigational drug product is routinely provided by the sponsor (Hengrui Medicine) at no charge to patients within the protocol. Travel, accommodation, and non-protocol medical costs remain the patient's responsibility.
Standard Treatment vs Clinical Trial
This comparison is for educational purposes. It is not a recommendation. All treatment decisions must be made with your oncologist.
How CancerFax Supports You
CancerFax is a global cancer navigation platform. For patients with advanced NEC โ one of the rarest and most underserved cancers in oncology โ we provide expert-led navigation toward the most promising available options.
The trial opens April 2026. CancerFax can review your pathology reports, Ki-67 index, prior treatment history, and tissue sample availability now โ so you are fully prepared and can submit on the first day enrollment opens. For patients with aggressive NEC, preparation time matters.
The two most clinically significant exclusions are prior CLDN18.2-targeted therapy and prior topoisomerase I inhibitor ADC. CancerFax can help clarify whether any of your prior treatments constitute these exclusions โ in particular, distinguishing irinotecan (small molecule, appears eligible) from topoisomerase I inhibitor ADCs (excluded).
A tumour tissue sample within 2 years is mandatory. CancerFax can advise on whether your archival tissue meets the requirement or whether a fresh biopsy is needed, and can help coordinate tissue preparation and shipping logistics for Prof. Ming Lu's team.
CancerFax can facilitate contact with Prof. Ming Lu's team (registered contact: Ming Lu MD, Beijing GoBroad Hospital, zip 100142) in advance of the trial opening โ to confirm eligibility questions and ensure your records are on file when enrollment begins.
Beijing GoBroad Hospital (zip 100142, Beijing Municipality) has infrastructure for international patients. For patients travelling from outside China, CancerFax provides medical visa guidance, accommodation near the Beijing GoBroad Hospital campus, interpreter coordination, and caregiver logistics for the Q3W infusion schedule.
If you do not meet this trial's eligibility criteria โ for example due to prior topo-I ADC history, ECOG 2 status, or excluded histological subtypes โ CancerFax can identify alternative active NEC trials, including Prof. Ming Lu's concurrent irinotecan liposome trial (NCT07014540) also at Beijing GoBroad Hospital, and international second-line NEC studies.
CancerFax does not guarantee trial enrollment or treatment outcome. Our role is to help patients access accurate information and appropriate pathways.
Questions to Ask Before Considering This Trial
If you speak with Prof. Ming Lu's team at Beijing GoBroad Hospital or discuss this trial with your oncologist, these questions will help guide the conversation.
Frequently Asked Questions
Advanced NEC After Platinum Failure โ Exploring New Options?
NCT07520357 is opening for enrollment in April 2026. For patients with advanced neuroendocrine carcinoma who have progressed on platinum-based chemotherapy, this Phase 2 trial of SHR-A1904 may be the most scientifically grounded new option currently entering clinical evaluation. Register your interest now so CancerFax can prepare your records before enrollment opens.
The information on this page is for educational and patient-navigation purposes only. It does not replace medical advice, diagnosis, or treatment from a qualified physician. Clinical trial eligibility, enrollment, treatment decisions, and costs are determined only by the trial investigators, hospital, sponsor, and applicable regulations. CancerFax helps patients and families understand options and coordinate case review where appropriate, but does not guarantee trial acceptance, treatment response, or clinical outcome. All clinical decisions must be made in consultation with a qualified, licensed physician with access to the patient's complete medical information.
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ยฉ CancerFax ยท Specialist cancer access and patient-navigation platform. CancerFax is not a medical institution, hospital, or clinical trial sponsor. Trial details may change; always confirm current eligibility, status, and costs directly with the trial center.