---
title: Phase 3 Clinical Study of AK112 for NSCLC Patients
nct_id: NCT05184712
overall_status: ACTIVE_NOT_RECRUITING
phase: PHASE3
sponsor: Akeso
study_type: INTERVENTIONAL
primary_condition: Non-Squamous Non-small Cell Lung Cancer
countries: China
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT05184712.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT05184712"
ct_last_update_post_date: 2026-03-04
last_seen_at: "2026-05-12T07:16:07.685Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# Phase 3 Clinical Study of AK112 for NSCLC Patients

**Official Title:** A Randomized, Double-blind, Multi-center, Phase III Study of AK112 Combined With Pemetrexed and Carboplatin Versus Placebo Combined With Pemetrexed and Carboplatin in Patients With Locally Advanced or Metastatic EGFR-mutant Non-squamous NSCLC Who Have Failed Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs)

**NCT ID:** [NCT05184712](https://clinicaltrials.gov/study/NCT05184712)

## Key Facts

- **Status:** ACTIVE_NOT_RECRUITING
- **Phase:** PHASE3
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 322
- **Lead Sponsor:** Akeso
- **Conditions:** Non-Squamous Non-small Cell Lung Cancer
- **Start Date:** 2022-01-25
- **Completion Date:** 2026-09
- **CT.gov Last Update:** 2026-03-04

## Brief Summary

A Randomized, Double-blind, Multi-center, Phase III Clinical Study of AK112 or Placebo Combined With Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Failed to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment

## Detailed Description

The trial will be performed as a randomized, Double-Blind, Multicenter trial to compare AK112 Plus Pemetrexed and Carboplatin to Placebo Plus Pemetrexed and Carboplatin in Patients with Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Harboring. Approximately 320 subjects will be randomized to the two treatment at the ratio of 1:1. Each enrolled subject will receive an intravenous infusion of the AK112/Placebo Plus Pemetrexed and Carboplatin （Q3W,up to 4 cycles）in treatment periods per the randomization schedule. Afterward, AK112/ Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

## Eligibility

- **Minimum age:** 18 Years
- **Maximum age:** 75 Years
- **Sex:** ALL
- **Healthy Volunteers:** No

```
Inclusion Criteria:

1. Ability to understand and voluntarily sign a written informed consent form (ICF), which must be signed before the specified study procedures required for the study are performed.
2. Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.
4. Life expectancy ≥3 months；
5. Locally advanced (stage IIIB/IIIC) or metastatic (stage IV) non-squamous NSCLC confirmed by histology or cytology, inoperable and unable to receive radiotherapy and chemotherapy;
6. The tumor histology, cytology or hematology confirmed the presence of EGFR activating mutations before enrollment
7. Have previously received EGFR-TKI treatment and the treatment has failed
8. Subjects have at least one measurable non-brain tumor lesion per RECIST v1.1
9. Major organ function prior to treatment meets the following criteria
10. Patients of childbearing potential must agree to use effective contraceptive measures

Exclusion Criteria:

1. Histological or cytological pathology confirmed the presence of small cell carcinoma components, or the main component is squamous cell carcinoma
2. There are reports confirming the existence of other driver gene mutations with known drug treatments
3. Subjects who received any prior treatments targeting the mechanism of tumor immunity
4. The subject has received systemic anti-tumor therapy other than EGFR-TKI
5. Currently enrolled in any other clinical study
6. Received EGFR-TKI treatment, palliative local treatment, non-specific immunomodulatory treatment within 2 weeks prior to the first dose; and Chinese herbal medicine or traditional Chinese medicinal products with anti-tumor indications within 1 weeks prior to the first dose.
7. Tumor surrounds important blood vessels or has obvious necrosis, cavitation, or invades surrounding important organs and blood vessels.
8. Symptomatic central nervous system metastases
9. Active malignancies within the past 3 years, with the exception of tumors in this study and cured local tumors
10. Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment
11. There is a history of major diseases 1 year prior to the first dose.
12. .Medical history of gastrointestinal perforation or gastrointestinal fistula within 6 months prior to the first dose
13. Received chest radiation therapy prior to the first dose
14. Presence of clinically symptomatic pleural effusion, pericardial effusion, or ascites requiring frequent drainage.
15. Active or previously documented inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis).
```

## Arms

- **Ivonescimab (SMT112 or AK112) in combination with Pemetrexed and Carboplatin** (EXPERIMENTAL) — Subjects will receive Ivonescimab (SMT112 or AK112) Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles. Afterward, AK112 Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.
- **Placebo in combination with Pemetrexed and Carboplatin** (PLACEBO_COMPARATOR) — Subjects will receive Placebo Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles in treatment periods per the randomization schedule. Afterward, Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

## Interventions

- **Ivonescimab (SMT112 or AK112) Injection** (DRUG) — Subjects will receive Ivonescimab (SMT112 or AK112) Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles. Afterward, Ivonescimab (SMT112 or AK112) Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.
- **Placebo Injection** (DRUG) — Subjects will receive Placebo Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles in treatment periods per the randomization schedule. Afterward, Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.

## Primary Outcomes

- **Progression-free survival (PFS)** _(time frame: Up to 2 years)_ — Progression-free survival (PFS) assessed by IRC per RECIST v1.1 in the ITT population.

## Secondary Outcomes

- **OS** _(time frame: Up to 2 years)_
- **ORR** _(time frame: Up to 2 years)_
- **DCR** _(time frame: Up to 2 years)_
- **DoR** _(time frame: Up to 2 years)_
- **TTR** _(time frame: Up to 2 years)_
- **PFS** _(time frame: Up to 2 years)_
- **AE** _(time frame: From the subject signs the ICF to 30 days (AE) and 90 days (SAE) after the last dose of study treatment or initiation of other anti-tumor therapy, whichever occurs first,up to 2 years)_
- **Observed concentrations of AK112** _(time frame: through study completion, an average of 2 year)_
- **Number of subjects who develop detectable anti-drug antibodies (ADAs)** _(time frame: From first dose of AK112 through 90 days after last dose of AK112,up to 2 years)_

## Locations (1)

- Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China

## Recent Field Changes (last 30 days)

- `status.overallStatus` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.maxAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.sun yat-sen university cancer center|guangzhou|guangdong|china` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT05184712.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT05184712*  
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