AK112 for Non-Small Cell Lung Cancer

Not currently recruiting at 78 trial locations

Overseen By Lori Styles, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Summit Therapeutics

Must not be taking: Immunotherapy, Chinese herbal

Disqualifiers: Small cell carcinoma, Other driver mutations, Active autoimmune, others

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 called AK112 (an injection) to determine its effectiveness for people with non-small cell lung cancer (NSCLC) that has specific mutations in the EGFR gene. The focus is on patients whose cancer has advanced and who have not responded to EGFR-targeted therapy. Participants will receive either AK112 with two chemotherapy drugs (Pemetrexed and Carboplatin) or a placebo with the same chemotherapy drugs. Individuals with locally advanced or metastatic non-squamous NSCLC, who have previously tried and not benefited from EGFR-targeted treatments, might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have received certain treatments like EGFR-TKI, palliative local treatment, or non-specific immunomodulatory treatment within 2 weeks before starting the trial. Check with the trial team for more details.

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

Research has shown that Ivonescimab, also known as AK112, is generally safe for humans. In earlier studies, patients with advanced or spreading non-small cell lung cancer who received Ivonescimab with chemotherapy did not experience more side effects than those who did not receive it. These studies found no significant increase in negative reactions, suggesting the treatment is relatively safe.

Another study demonstrated good results when using Ivonescimab with chemotherapy, without major safety issues. This is encouraging for those considering trials with AK112. While all treatments carry some risk, current evidence suggests that Ivonescimab is a safe choice for many patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Researchers are excited about Ivonescimab (AK112) for non-small cell lung cancer because it offers a novel approach compared to traditional treatments like pembrolizumab or nivolumab, which target PD-1/PD-L1 pathways. Ivonescimab is a bispecific antibody that simultaneously targets both PD-1 and VEGF, potentially enhancing anti-tumor activity and improving patient outcomes by addressing tumor growth and immune evasion more effectively. Moreover, the combination of Ivonescimab with chemotherapy agents like Pemetrexed and Carboplatin might enhance its efficacy, potentially leading to better results than existing monotherapies. This innovative mechanism and combination approach are why researchers are optimistic about its potential in treating non-small cell lung cancer.

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

Research has shown that Ivonescimab (AK112), one of the treatments in this trial, when combined with chemotherapy, yields promising results for advanced lung cancer. Studies found a 40% lower risk of the cancer worsening or causing death compared to Tislelizumab, another treatment used with chemotherapy. This combination proved especially effective for patients with higher levels of a protein called PD-L1. The treatment demonstrated good survival rates and was generally safe for patients. These findings suggest that Ivonescimab could be an effective option for those who haven't succeeded with other lung cancer treatments. Participants in this trial will receive either Ivonescimab with Pemetrexed and Carboplatin or a placebo with the same chemotherapy regimen. ^{1 4 5 6 7}

Who Is on the Research Team?

Li Zhang, MD

Principal Investigator

Sun Yat-sen University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced non-squamous NSCLC that has worsened after EGFR-TKI treatment. They must have good organ function, an ECOG score of 0 or 1, a life expectancy of at least three months, and agree to use contraception. Exclusions include other treatable gene mutations, recent treatments conflicting with the study drugs, symptomatic brain metastases, significant health issues within the last year, active severe diseases or participation in another clinical study.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

You are expected to live for at least 3 more months.

I have taken a 3rd generation EGFR-TKI treatment and my cancer progressed after that.

Exclusion Criteria

I have brain metastases causing symptoms.

I haven't had any cancer except for my current one or any cured local tumors in the past 3 years.

I have received cancer treatment that is not EGFR-TKI.

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 AK112 or Placebo combined with Pemetrexed for maintenance treatment 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

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• AK112 Injection
• Placebo Injection

Trial Overview The trial tests Ivonescimab (AK112) plus chemotherapy against a placebo plus chemotherapy in patients whose lung cancer progressed after previous treatments. It's randomized and double-blind meaning neither participants nor researchers know who gets the real drug versus placebo until after results are analyzed.

How Is the Trial Designed?

Group I: Ivonescimab (SMT112 or AK112) in combination with Pemetrexed and Carboplatin Experimental Treatment 1 Intervention

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.

Group II: Placebo in combination with Pemetrexed and Carboplatin Placebo Group 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

Lead 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/lancet/article/PIIS0140-6736(25)02172-5/fulltext?rss=yes

Progress in outcomes for patients with metastatic ... The use of immunotherapy in patients with various types of cancer has led to dramatic increases in survival. Increased median survival and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06928389

Study Details | NCT06928389 | Ivonescimab in ... The purpose of this study is to evaluate the efficacy and safety of ivonescimab versus placebo, combined with docetaxel in patients with advanced NSCLC.

3. onclive.com onclive.com/view/ivonescimab-plus-chemo-might-be-a-new-soc-in-advanced-squamous-nsclc

Ivonescimab Plus Chemo Might Be a New SOC ... Ivonescimab plus chemotherapy improved PFS and response rates vs tislelizumab in advanced squamous NSCLC, with a manageable safety profile.

4. 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 ...

5. smmttx.com smmttx.com/pressrelease/ivonescimab-with-chemotherapy-reduced-the-risk-of-disease-progression-or-death-by-40-compared-to-tislelizumab-pd-1-inhibitor-plus-chemotherapy-in-1l-treatment-of-patients-with-squamous-nsclc-in-the/

Ivonescimab with Chemotherapy Reduced the Risk ... Ivonescimab with Chemotherapy Reduced the Risk of Disease Progression or Death by 40% Compared to Tislelizumab (PD-1 Inhibitor) Plus ...

6. akesobio.com akesobio.com/en/media/akeso-news/250423/

Akeso, Inc | Ivonescimab in Combination with ... In patients with up to 63% central squamous carcinoma, ivonescimab demonstrated a safety profile comparable to the control group. This ...

7. 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.