A Phase IIa Study Evaluating Injectable ALK-N001 in Patients With Advanced Gastrointestinal Tumors

An Open-label, Multicenter Phase IIa Study to Evaluate the Efficacy and Safety of Injectable ALK-N001 in Patients With Advanced Gastrointestinal Tumors

This open-label, multicenter Phase IIa study is to evaluate the efficacy and safety of injectable ALK-N001 in patients with advanced gastrointestinal tumors, with the primary objective to assess its preliminary efficacy.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Gastrointestinal Tumors
• Intervention / Treatment: Drug: Injectable ALK-N001

• Study Type: Interventional
• Enrollment (Estimated): 174
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily sign informed consent, understand the study and be willing and able to comply with all study procedures.
2. Age ≥18 years (male or female) at the time of signing informed consent.
3. Histologically or cytologically confirmed locally advanced or metastatic esophageal squamous cell carcinoma, colorectal adenocarcinoma, or other gastrointestinal tumors.

4. Disease progression or intolerance after prior standard-of-care (SoC) treatment:

   1. Cohort1 (ESCC): Not eligible for curative surgery/radiochemotherapy; progressed or intolerant after at least 1st-line platinum-based chemotherapy plus PD-(L)1 inhibitor. If immunotherapy is declined/ineligible, progressed after ≥2 lines of systemic therapy.
   2. Cohort2 (CRC): Received standard systemic therapy for metastatic colorectal cancer and experienced progression or intolerance. Must have received fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy (±bevacizumab/cetuximab), unless contraindicated. For MSI-H/dMMR tumors, prior PD-(L)1 inhibitor is required.
   3. Cohort3 (Other GI tumors): Not curable by surgery; disease progression/intolerance after standard-of-care therapy, or no available effective treatment.
5. At least one measurable lesion per RECIST V1.1 (lesions in prior radiation field generally not measurable unless clear progression).
6. ECOG performance status 0 or 1.
7. Expected survival ≥3 months.

8. Adequate organ function:

   • Bone marrow (no transfusion/growth factors within prior 14 days): ANC ≥1.5×10⁹/L; PLT ≥90×10⁹/L; Hb ≥90 g/L
   • Liver: TBIL ≤1.5×ULN; ALT ≤3×ULN (≤5×ULN for liver metastasis); AST ≤3×ULN (≤5×ULN for liver metastasis); ALB ≥35 g/L
   • Renal: Cr ≤1.5×ULN; if Cr>1.5×ULN, CrCl ≥50 mL/min (Cockcroft-Gault formula)
   • Coagulation: APTT ≤1.5×ULN; INR ≤1.5×ULN
9. Women of childbearing potential must have negative pregnancy test at screening and agree to effective contraception or abstinence from consent until 6 months after last dose. Male participants must use effective contraception or abstinence from consent until 6 months after last dose; no sperm donation.

Exclusion Criteria:

• 1. Received chemotherapy, radiotherapy (palliative local radiotherapy within prior 2 weeks), biotherapy, targeted therapy, immunotherapy, TIL or other anti-tumor therapies within 4 weeks before first dose.

  1. Anti-endocrine therapy within 2 weeks or 5 half-lives; oral CDK4/6i, small molecule targeted agents, anti-tumor Chinese medicine.
  2. CAR-T, CAR-NK or tumor vaccine within prior 3 months.
  3. Live vaccine within 2 weeks; non-live vaccine within 4 weeks before first dose.

  4. Investigational drug within 4 weeks or 5 half-lives before first dose (whichever shorter).

     2. Use of strong CYP3A4 inducer/inhibitor within 7 days before first dose or planned during study.

     3. Prior treatment with DXD-containing ADC or PDC. 4. Active infection at screening requiring systemic anti-infective therapy within 2 weeks prior to first dose.

     5. Known BRAF mutation or NTRK fusion positive colorectal cancer (Cohort2). 6. Unstable or progressive CNS/leptomeningeal metastases (stable brain metastases ≥1 month, no new/enlarging lesions and off steroids ≥4 weeks may enroll).

     7. Clinically uncontrolled third-space effusion requiring therapeutic paracentesis/drainage within prior 14 days.

     8. Prior or current interstitial lung disease (ILD), non-infectious pneumonitis requiring steroids, suspected ILD or severely impaired pulmonary function.

     9. Severe GI disease including chronic inflammatory bowel disease, bowel obstruction or chronic diarrhea.

     10. Esophageal stent placement, tracheal stent or esophageal stricture (Cohort1).

     11. Severe cardiovascular disease:

  1. Clinically significant cardiac arrhythmias or 2nd/3rd degree AV block requiring intervention.
  2. Acute coronary syndrome, heart failure, stroke or grade ≥3 cardiovascular event within 6 months.
  3. NYHA Class ≥II heart failure (exception: stable NYHA II, LVEF≥50%, no exacerbation ≥6 months after optimized medical treatment, confirmed by cardiologist).

  4. Uncontrolled hypertension: SBP≥150 mmHg and/or DBP≥100 mmHg. 12. History of GI perforation/fistula within 6 months before first dose, or tumor invading adjacent organs (great vessel/trachea) with high risk of bleeding/fistula.

     13. History of severe thromboembolism within prior 6 months; known inherited/acquired thrombophilia.

     14. Other malignancy within past 5 years (exception: cured cervical carcinoma in situ, cutaneous squamous cell carcinoma, basal cell carcinoma, papillary thyroid carcinoma).

     15. Prior allogeneic hematopoietic stem cell or solid organ transplantation. 16. Prior anti-tumor adverse events not recovered to ≤ Grade1 (NCI-CTCAE v6.0, alopecia and investigator-assessed non-risk toxicities excluded) or not meeting eligibility lab criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (ESCC), Dose A (37.5 mg/m²); Participants with advanced esophageal squamous cell carcinoma (ESCC) receive injectable ALK-N001 at 37.5 mg/m² intravenously every 2 weeks (Q2W) per 28-day cycle. Enrollment and dose expansion may be adjusted by the Safety Review Committee (SRC) based on accumulated safety, PK, PD and preliminary anti-tumor data. Treatment continues until intolerable toxicity, progressive disease, or other discontinuation criteria.	Drug: Injectable ALK-N001; Injectable ALK-N001 is administered intravenously every 2 weeks (Q2W; 28-day treatment cycle). Two predefined dose levels are available: 37.5 mg/m² (Dose A) and 50 mg/m² (Dose B). Enrollment or suspension of dose groups may be determined by the Safety Review Committee (SRC) based on safety, PK, PD and preliminary anti-tumor activity data.; Other Names: QHL-1618
Experimental: Cohort 1 (ESCC), Dose B (50 mg/m²); Participants with advanced esophageal squamous cell carcinoma (ESCC) receive injectable ALK-N001 at 50 mg/m² intravenously every 2 weeks (Q2W) per 28-day cycle. Enrollment and dose expansion may be adjusted by the Safety Review Committee (SRC) based on accumulated safety, PK, PD and preliminary anti-tumor data. Treatment continues until intolerable toxicity, progressive disease, or other discontinuation criteria.	Drug: Injectable ALK-N001; Injectable ALK-N001 is administered intravenously every 2 weeks (Q2W; 28-day treatment cycle). Two predefined dose levels are available: 37.5 mg/m² (Dose A) and 50 mg/m² (Dose B). Enrollment or suspension of dose groups may be determined by the Safety Review Committee (SRC) based on safety, PK, PD and preliminary anti-tumor activity data.; Other Names: QHL-1618
Experimental: Cohort 2 (CRC), Dose A (37.5 mg/m²); Participants with advanced colorectal carcinoma (CRC) receive injectable ALK-N001 at 37.5 mg/m² intravenously every 2 weeks (Q2W) per 28-day cycle. Enrollment and dose expansion may be adjusted by the Safety Review Committee (SRC) based on accumulated safety, PK, PD and preliminary anti-tumor data. Treatment continues until intolerable toxicity, progressive disease, or other discontinuation criteria.	Drug: Injectable ALK-N001; Injectable ALK-N001 is administered intravenously every 2 weeks (Q2W; 28-day treatment cycle). Two predefined dose levels are available: 37.5 mg/m² (Dose A) and 50 mg/m² (Dose B). Enrollment or suspension of dose groups may be determined by the Safety Review Committee (SRC) based on safety, PK, PD and preliminary anti-tumor activity data.; Other Names: QHL-1618
Experimental: Cohort 2 (CRC), Dose B (50 mg/m²); Participants with advanced colorectal carcinoma (CRC) receive injectable ALK-N001 at 50 mg/m² intravenously every 2 weeks (Q2W) per 28-day cycle. Enrollment and dose expansion may be adjusted by the Safety Review Committee (SRC) based on accumulated safety, PK, PD and preliminary anti-tumor data. Treatment continues until intolerable toxicity, progressive disease, or other discontinuation criteria.	Drug: Injectable ALK-N001; Injectable ALK-N001 is administered intravenously every 2 weeks (Q2W; 28-day treatment cycle). Two predefined dose levels are available: 37.5 mg/m² (Dose A) and 50 mg/m² (Dose B). Enrollment or suspension of dose groups may be determined by the Safety Review Committee (SRC) based on safety, PK, PD and preliminary anti-tumor activity data.; Other Names: QHL-1618
Experimental: Cohort 3 (Other GI Tumors), Dose A (37.5 mg/m²); Participants with advanced other gastrointestinal tumors receive injectable ALK-N001 at 37.5 mg/m² intravenously every 2 weeks (Q2W) per 28-day cycle. Cohort 3 is exploratory and will be activated only if meaningful anti-tumor signals are observed in concurrent ALK-N001 trials. SRC may adjust enrollment based on safety, PK, PD and efficacy data. Treatment continues until intolerable toxicity, progressive disease, or other discontinuation criteria.	Drug: Injectable ALK-N001; Injectable ALK-N001 is administered intravenously every 2 weeks (Q2W; 28-day treatment cycle). Two predefined dose levels are available: 37.5 mg/m² (Dose A) and 50 mg/m² (Dose B). Enrollment or suspension of dose groups may be determined by the Safety Review Committee (SRC) based on safety, PK, PD and preliminary anti-tumor activity data.; Other Names: QHL-1618
Experimental: Cohort 3 (Other GI Tumors), Dose B (50 mg/m²); Participants with advanced other gastrointestinal tumors receive injectable ALK-N001 at 50 mg/m² intravenously every 2 weeks (Q2W) per 28-day cycle. Cohort 3 is exploratory and will be activated only if meaningful anti-tumor signals are observed in concurrent ALK-N001 trials. SRC may adjust enrollment based on safety, PK, PD and efficacy data. Treatment continues until intolerable toxicity, progressive disease, or other discontinuation criteria.	Drug: Injectable ALK-N001; Injectable ALK-N001 is administered intravenously every 2 weeks (Q2W; 28-day treatment cycle). Two predefined dose levels are available: 37.5 mg/m² (Dose A) and 50 mg/m² (Dose B). Enrollment or suspension of dose groups may be determined by the Safety Review Committee (SRC) based on safety, PK, PD and preliminary anti-tumor activity data.; Other Names: QHL-1618

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR), assessed per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	ORR is defined as the proportion of participants with confirmed complete response (CR) or partial response (PR) as evaluated by RECIST V1.1.	Up to approximately 24 months from the first dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	Description: DOR is defined as the time from the first documentation of CR/PR until the first documented progressive disease (PD) or death from any cause.	Up to approximately 24 months from the first dose.
Disease Control Rate (DCR)	DCR is the proportion of participants achieving CR, PR, or stable disease (SD) per RECIST V1.1. Time Frame: Up to approximately 24 months from the first dose.	Up to approximately 24 months from the first dose.
Progression-Free Survival (PFS)	PFS is the time from study enrollment to documented PD or death from any cause. 6-,12-,24-month PFS rates will be calculated.	Up to approximately 24 months from the first dose.
Overall Survival (OS)	OS is defined as the time from enrollment to death from any cause. 12-,24-month OS rates will be calculated.	Up to approximately 24 months from the first dose.
Safety (Adverse Events and Serious Adverse Events)	Incidence, severity and relatedness of AEs and SAEs; laboratory tests, 12-lead ECG, vital signs, physical examination and ECOG performance status.	From informed consent until 28±7 days after last dose.
Population Pharmacokinetics (PopPK) of total DXD and free DXD	Characterize PopPK profiles of total DXD and free DXD.	From first dose up to end of treatment.
Exposure-Response (E-R) relationship of total DXD and free DXD	E-R relationship between total/free DXD exposure and efficacy, safety and biomarkers.	From first dose up to approximately 24 months after first dose.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expression level of Legumain in tumor tissue	Tumor tissue samples (fresh biopsy or archived paraffin-embedded tissue) will be collected from all participants at screening (mandatory) and at disease progression (optional) for central laboratory Legumain testing. Previous genetic or protein testing reports will be collected if available. Evaluate the correlation between tumor Legumain expression and anti-tumor efficacy.	Screening (mandatory baseline sample collection); optional sampling at disease progression; analysis up to approximately 24 months after the first dose.

Collaborators and Investigators

• Sponsor: Zhejiang Anglikang Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: September 13, 2026
• First Submitted That Met QC Criteria: September 13, 2026
• First Posted (Actual): September 17, 2026

Study Record Updates

• Last Update Posted (Actual): September 17, 2026
• Last Update Submitted That Met QC Criteria: September 13, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Phase IIa; Advanced Gastrointestinal Tumors; ALK-N001
• Other Study ID Numbers: ALK-N001-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No