AK112 for Non-Small Cell Lung Cancer

Not currently recruiting at 81 trial locations

Overseen By Lori Styles, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Summit Therapeutics

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Small cell carcinoma, Squamous cell carcinoma, Active autoimmune disease, Severe infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, AK112 (an experimental treatment), for individuals with non-small cell lung cancer (NSCLC) that has advanced or spread and contains specific mutations in the EGFR gene. Researchers aim to determine if AK112, combined with standard cancer drugs pemetrexed and carboplatin, is more effective than a placebo with these drugs. Ideal candidates for this trial are those whose cancer has worsened after taking specific EGFR-targeting medicines. Participants must have non-squamous NSCLC, and their tumors should not be removable by surgery. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants early access to potentially effective treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking EGFR inhibitor therapy at least 2 weeks before the first dose, except for osimertinib, which should be stopped 7 days prior. Other medications, like nonspecific immunomodulatory therapy and certain Chinese medicines, also need to be stopped before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AK112, also known as ivonescimab, is generally safe for patients with non-small cell lung cancer. Studies indicate that AK112 can be safely combined with chemotherapy. Most patients tolerate the treatment well, and any side effects are manageable. Specifically, one study found that AK112 is safe for patients with advanced stages of this cancer. While some side effects may occur, they are not severe and can be effectively managed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AK112 for non-small cell lung cancer because it combines a novel anti-PD-1/VEGF bispecific antibody with existing chemotherapy agents, Pemetrexed and Carboplatin. Unlike the standard treatments that typically focus on either PD-1 inhibitors or chemotherapy alone, AK112 targets both the PD-1 pathway, which helps tumors evade the immune system, and the VEGF pathway, which is involved in tumor blood vessel growth. This dual targeting approach has the potential to enhance the immune system's ability to fight cancer while simultaneously disrupting the tumor's blood supply, offering a potentially more effective treatment option.

What evidence suggests that AK112 could be an effective treatment for non-small cell lung cancer?

Research has shown that AK112, a new treatment, may aid in treating advanced non-small cell lung cancer (NSCLC). In this trial, some participants will receive AK112 combined with Pemetrexed and Carboplatin. Studies have found that AK112 with chemotherapy can significantly reduce tumor size. In one study, patients who received AK112 lived longer than those who received standard treatments. Early results also suggest that AK112 can be safely used with chemotherapy. Overall, these findings support the potential of AK112 in treating NSCLC. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-squamous NSCLC that has worsened after EGFR-TKI treatment. Participants must be in good physical condition, have measurable cancer, and acceptable organ function. They can't join if they've had certain other cancers, serious heart conditions, immune diseases or lung issues unrelated to their cancer.

Inclusion Criteria

At least 1 measurable noncerebral lesion according to RECIST v1.1

Expected survival ≥3 months

Ability to understand and voluntarily sign a written informed consent form (ICF)

Exclusion Criteria

Concurrent enrollment in another clinical study

Imaging showing tumor characteristics

I have recently had radiation therapy on my chest or another part of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AK112 or Placebo combined with Pemetrexed and Carboplatin via intravenous infusion every 3 weeks, up to 4 cycles

12 weeks

4 visits (in-person)

Maintenance Treatment

Participants receive maintenance treatment with AK112 or Placebo plus Pemetrexed every 3 weeks, up to 2 years

up to 2 years

Regular visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• AK112

Trial Overview The study tests AK112 injection versus a placebo. Both are given alongside standard chemotherapy drugs Pemetrexed and Carboplatin. It's randomized and double-blind, meaning neither the patients nor doctors know who gets AK112 or the placebo.

How Is the Trial Designed?

Group I: AK112 in combination with Pemetrexed and Carboplatin Experimental Treatment 1 Intervention

Subjects will receive 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.

Group II: Placebo in combination with Pemetrexed and Carboplatin Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

Summit Therapeutics

Lead Sponsor

Trials

18

Recruited

4,500+

Akeso

Industry Sponsor

Trials

122

Recruited

23,400+

Dr. Simon Williams

Akeso

Chief Executive Officer since 2022

PhD in Organic Chemistry from Cambridge University

Dr. Baiyong Li

Akeso

Chief Medical Officer

MD from an unspecified institution

Citations

1. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00283-3/fulltext

AK112, a novel PD-1/VEGF bispecific antibody, in ... This study aimed to evaluate the efficacy and safety of AK112 combined with chemotherapy in patients with advanced non-small cell lung cancer ( ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05499390

NCT05499390 | AK112 in Advanced Non-Small Cell Lung ... The purpose of this study is to evaluate the efficacy and safety of AK112 comparing Pembrolizumab in subjects with advanced NSCLC.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.9087

Phase II results of ivonescimab (AK112/ SMT112), a novel ... Ivonescimab, plus chemotherapy has shown promising anti-tumor activity in pts with advanced/metastatic NSCLC without AGA and can be administered safely.

4. smmttx.com smmttx.com/pressrelease/https-www-smmttx-com-wp-content-uploads-2025-04-2025_pr_0425_ivonescimab-ak112-303-approval-_-final-pdf/

Interim Analysis of HARMONi-2 Shows an Overall Survival ... Interim Analysis of HARMONi-2 Shows an Overall Survival Hazard Ratio of 0.777 Favoring Ivonescimab at 39% Data Maturity, ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT367566

A phase Ib/II study of AK112, a PD-1/VEGF bispecific ... AK112 is a humanized IgG1 bispecific antibody against PD-1 and VEGF. Here, we reported results of an ongoing phase Ib/II trial of AK112 in advanced NSCLC pts.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11818946/

Efficacy and Safety of Ivonescimab in the Treatment ... Ivonescimab showed promising antitumor activity and improved clinical outcomes, particularly in patients with higher PD-L1 expression levels and those ...

7. akesobio.com akesobio.com/media/2293/wclc-2024-presentation-ak112-303-final.pdf

Phase 3 Study of Ivonescimab (AK112) vs. Pembrolizumab ... ... NSCLC, non-small cell lung cancer. PD-L1 High (TPS ≥50%). PD-L1 Low (TPS 1 ... Ivonescimab also demonstrated tolerable safety profile in SQ patients. Safety ...