Global, Multicenter Study of AMT-116 Versus Investigator's Choice in Participants With Advanced or Metastatic Non-squamous EGFR-Wildtype Non-Small Cell Lung Cancer (NSCLC) With Progression on or After Platinum-Based Chemotherapy and Anti-PD-1/PD-L1 Immunotherapy

NCT07718737 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: AMT-116-201
• Study Type: interventional
• Target: 512
• Locations: 1 country
• Sites: 5

Brief Summary

This clinical trial consists of two parts: phase 2 and phase 3. The goal of phase 2 of this clinical trial is to compare which dose level of AMT-116 works better to treat advanced or metastatic non-squamous EGFR-Wildtype non-small cell lung cancer (NSCLC) in adults. It will also learn about the safety of AMT-116. The main questions it aims to answer are:

• Which level of AMT-116 works better to treat advanced or metastatic non-squamous EGFR-Wildtype NSCLC?
• What medical problems do participants have when taking AMT-116? The goal of phase 3 of this clinical trial is to compare AMT-116 to study doctor's choice (a kind of retainable treatment for you in the opinion of the study doctor) to see if AMT-116 works better to treat advanced or metastatic non-squamous EGFR-Wildtype NSCLC. In both parts of this trial, participants will receive AMT-116 or study doctor's choice every 2 weeks until the study doctor thinks you are benefiting from your participation or until your disease progresses or you are unable to tolerate the study drug

Conditions

NSCLC (Advanced Non-small Cell Lung Cancer)

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events as Assessed by CTCAE v6.0

  About 7 months

Secondary Outcomes (9)

• Objective response rate (ORR)

  About 6 months

• Progression free survival (PFS)

  About 6 months

• Duration of response (DOR)

  About 6 months

• Disease control rate (DCR)

  About 6 months

• Peak and pre-dose trough concentrations (Cmax and Ctrough) over time for conjugated antibody

  About 6 months

Other Outcomes (4)

• Correlation of PFS with baseline tumor CD44v9 expression

  About 12 months

• Correlation of ORR with baseline tumor CD44v9 expression

  About 12 months

• Correlation of DOR with baseline tumor CD44v9 expression

  About 12 months

Study Arms (3)

AMT-116 4 mg/kg

EXPERIMENTAL

Drug: AMT-116

AMT-116 5 mg/kg

EXPERIMENTAL

Drug: AMT-116

Investigator's choice of therapy (docetaxel or docetaxel plus ramucirumab)

ACTIVE COMPARATOR

Drug: Investigator's choice regimens (docetaxel or docetaxel plus ramucirumab)

Interventions

AMT-116 DRUG

AMT-116 will be administered at 4 mg/kg or 5 mg/kg as an intravenous (IV) infusion on Day 1 of each 2-week cycle.

AMT-116 4 mg/kg; AMT-116 5 mg/kg

Investigator's choice regimens (docetaxel or docetaxel plus ramucirumab) DRUG

Docetaxel will be administered as an IV infusion of 75 mg/m2 over approximately 60 minutes on Day 1 of each 3-week cycle. Ramucirumab will be administered as an IV infusion of 10 mg/kg over 30-60 minutes on Day 1 of each 3-week cycle prior to docetaxel

Investigator's choice of therapy (docetaxel or docetaxel plus ramucirumab)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily agree to join this clinical trial, sign the informed consent form, and follow all trial arrangements, including scheduled hospital visits, examinations and other study requirements.
• Age between 18 and 80 years old (including 18 and 80 years old) at the time of signing the informed consent form.
• Diagnosed with non-squamous non-small cell lung cancer (NSCLC) confirmed by pathological or cytological tests. The disease must be either locally advanced and unresectable (not suitable for radical chemoradiotherapy) or metastatic advanced lung cancer.
• Must have a clear EGFR gene test result before enrollment. Patients with other actionable gene mutations (excluding EGFR mutation) are eligible. Testing for other genes is not mandatory, and can be performed according to local hospital routine standards and available treatment options.
• Have received no more than one line of chemotherapy for advanced or metastatic lung cancer. Neoadjuvant or adjuvant chemotherapy will be counted as one prior chemotherapy line if the disease progresses within 6 months after the end of treatment.
• Have received at least one prior formal treatment (chemotherapy, targeted therapy or immunotherapy) for advanced or metastatic lung cancer, with subsequent disease progression or recurrence. Participants must meet the corresponding requirements based on their genetic status:
• Patients without any actionable gene mutations: Have experienced disease progression after platinum-based chemotherapy and immune checkpoint inhibitor therapy (used alone or combined with chemotherapy), or are not suitable for the above two treatments clinically.
• Patients with gene mutations that do not routinely use immunotherapy (e.g., ALK fusion): Have experienced disease progression after targeted therapy for gene mutations and platinum-based chemotherapy, or are not suitable for the above two treatments clinically.
• Patients with gene mutations for which immunotherapy is a conventional treatment: Have also experienced disease progression after immune checkpoint inhibitor therapy (used alone or combined with chemotherapy), or are not suitable for immunotherapy clinically.
• The investigator confirms that the patient is suitable for docetaxel treatment (only applicable for Phase 3 trial).
• Have at least one measurable tumor lesion assessed by RECIST 1.1 criteria.
• ECOG physical status score is 0 or 1, with normal daily physical activity.
• Expected survival time is at least 12 weeks.
• Have normal and stable organ function. No blood transfusion, erythropoietin, thrombopoietin, granulocyte colony-stimulating factor or other supportive treatment within 14 days before the test, and meet the following laboratory standards:
• Blood routine: Absolute neutrophil count ≥ 1.5 × 10/L; platelet count ≥ 100 × 10/L; hemoglobin ≥ 90 g/L

You may not qualify if:

• Prior treatment with antibody-drug conjugates (ADCs) based on topoisomerase 1 inhibitors.
• Receipt of any systemic anti-cancer therapy within the shorter period between five half-lives of the drug or 21 days prior to randomization is prohibited.
• Notes:
• ① If the half-life of an investigational agent has not been determined, its administration within 21 days prior to randomization is not allowed.
• ② Patients receiving bisphosphonates or denosumab may continue these medications during the study and are not excluded.
• Tumor pathology confirms adenosquamous, neuroendocrine, or sarcomatoid features.
• Presence of actionable activating mutations in the epidermal growth factor receptor (EGFR) gene.
• Non-small cell lung cancer (NSCLC) patients who are eligible for definitive local therapy alone (e.g., selected stage IIIA patients) are excluded.
• Central nervous system (CNS) metastases:
• ① Patients with CNS metastases are eligible only if all the following conditions are fully met: the CNS metastases have been treated with surgical resection and/or radiotherapy at least 28 days prior to randomization; and post-treatment evaluation satisfies all three requirements below: (1) No cerebral edema is observed in screening examinations, and no ongoing need for systemic steroids or anticonvulsant medications; (2) Neurological symptoms are absent or stable (Grade ≤ 1); (3) Follow-up imaging conducted within 28 days prior to randomization shows no progression of treated lesions and no new lesions.
• ② Note: Patients with a history of leptomeningeal disease are strictly excluded.
• Unresolved toxicities of Grade \> 1 caused by prior systemic anti-cancer treatment.
• Note: Patients with Grade ≤ 2 peripheral neuropathy, alopecia of any grade, endocrinopathy well-managed by hormone replacement therapy, or other toxicities judged to pose no safety risks by the investigator are eligible for enrollment.
• Receipt of wide-field radiotherapy (e.g., irradiation covering more than 30% of bone marrow-bearing bones) within 28 days prior to randomization, or palliative radiotherapy for symptom control within 2 weeks prior to randomization.
• Undergoing major surgery (excluding vascular access device placement and tumor biopsy) within 28 days prior to randomization, or failure to fully recover from postoperative side effects of such surgery.

Sponsors & Collaborators

• Multitude Therapeutics Inc.: lead

Study Sites (5)

Coffs Harbour Health Campus

Coffs Harbour, Australia

Location

Austin Health (Olivia Newton John Cancer Centre)

Melbourne, Australia

Location

St Vincent's Hospital Melbourne

Melbourne, Australia

Location

Calvary Mater Newcastle

Newcastle, Australia

Location

Macquarie University Hospital

Sydney, Australia

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Docetaxel; Ramucirumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Yanhong Fu

CONTACT

+86 13952922547; yanhong.fu@multitudetherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2026
• First Posted: July 22, 2026
• Study Start (Estimated): August 28, 2026
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: July 22, 2026

Record last verified: 2026-07

Locations

AU (5)