Ivonescimab + Dato-DXd/Osimertinib for Lung Cancer

Recruiting at 6 trial locations

Overseen By Helena Yu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Anticoagulants, Antiplatelet agents

Disqualifiers: Pregnancy, Hypertension, Autoimmune disorders, others

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

Compensation: Varies

Number of Visits: 6

Duration: 1 year

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of combining ivonescimab (an experimental treatment) with either datopotamab deruxtecan (Dato-DXd) or osimertinib for treating non-small cell lung cancer (NSCLC) with an EGFR mutation. Researchers will explore the best dose combinations to minimize side effects and improve treatment outcomes. Suitable participants have previously received treatment for NSCLC with an EGFR mutation and continue to face challenges despite prior treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

Studies have shown that combining ivonescimab with either datopotamab deruxtecan (Dato-DXd) or osimertinib is generally safe for people with non-small cell lung cancer (NSCLC). Research indicates that the combination of ivonescimab and Dato-DXd results in a 35% response rate, meaning 35% of patients saw their tumors shrink. Additionally, 78% of patients experienced disease control, meaning their cancer did not worsen. The most common side effects involve blood-related issues, but these are usually manageable.

For the combination of ivonescimab and osimertinib, studies suggest it significantly extends the time patients live without their disease worsening. The safety was acceptable, with no unexpected serious side effects reported. Both combinations are undergoing further study to better understand their safety and effectiveness in treating NSCLC with an EGFR mutation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ivonescimab because it offers a novel approach to treating lung cancer. Unlike traditional therapies, which often focus on standard chemotherapy or targeted therapies like gefitinib or erlotinib, ivonescimab works by combining with other agents like Dato-DXd or osimertinib to enhance its effectiveness. This combination might improve outcomes by targeting cancer cells more precisely and reducing resistance to treatment. Additionally, ivonescimab's innovative mechanism as a bispecific antibody could potentially offer a more effective and personalized treatment option, setting it apart from existing therapies.

What evidence suggests that this trial's treatments could be effective for non-small cell lung cancer with an EGFR mutation?

This trial will evaluate two different treatment combinations for non-small cell lung cancer (NSCLC) with EGFR mutations. In one arm, participants will receive ivonescimab combined with datopotamab deruxtecan (Dato-DXd). Research has shown that this combination may be promising, as a study found that datopotamab deruxtecan significantly improved overall survival compared to standard chemotherapy. Additionally, ivonescimab, when used with chemotherapy, delayed cancer progression by 40% compared to other treatments.

In another arm, participants will receive ivonescimab combined with osimertinib. Research suggests that this pairing may extend the time patients live without their disease worsening, especially for those who have not responded to previous EGFR-TKI treatments. Osimertinib alone has also been shown to increase overall survival rates in treated patients. Overall, these combinations could offer effective treatment options for patients with this type of lung cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Helena Yu, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Inclusion Criteria

I am able to swallow pills or oral medications.

My organs and blood tests are within normal limits.

I have at least one tumor that can be measured and has not been treated with radiation.

Exclusion Criteria

I have had another type of cancer before, except for certain allowed cases.

I do not have active or bleeding brain metastases and do not need brain radiation soon.

My imaging shows my tumor has invaded major blood vessels or nearby organs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of Dato-DXd or Osimertinib with a fixed dose of Ivonescimab to determine the maximum tolerated dose

3-6 weeks

3 visits (in-person) for cohort A, 6 visits (in-person) for cohort B

Treatment

Participants receive the determined dose of Ivonescimab with Dato-DXd or Osimertinib every 3 weeks

1 year

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ivonescimab

How Is the Trial Designed?

Group I: Cohort B (Ivonescimab + Osimertinib) Phase IB Experimental Treatment 2 Interventions

3 + 3 escalation (2 dose levels)

Group II: Cohort B (Ivonescimab + Osimertinib) (Phase II) Experimental Treatment 2 Interventions

Ivonescimab every 3 weeks + Osimertinib daily

Group III: Cohort A (ivonescimab + Dato-DXd) Phase IA Experimental Treatment 2 Interventions

3 + 3 escalation (2 dose levels)

Group IV: Cohort A (ivonescimab + Dato-DXd) (Phase II) Experimental Treatment 2 Interventions

Every 3 weeks

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Summit Therapeutics

Industry Sponsor

Trials

18

Recruited

4,500+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07535437

A Study of Ivonescimab in Combination With Dato-DXd or ...

The researchers are doing this study to find out whether ivonescimab in combination with datopotamab deruxtecan- (Dato-DXd) or osimertinib ...

2.

mskcc.org

mskcc.org/cancer-care/clinical-trials/25-366

A Study of Ivonescimab in Combination With DatoDXd ...

Full Title A Phase 1/2 Trial of Ivonescimab with Dato-DXd or Osimertinib in Patients with Metastatic EGFR-Mutant Non-Small Cell Lung Cancer that Progressed ...

3.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2026-03044

Ivonescimab with Dato-DXd or Osimertinib for the ...

Giving ivonescimab with Dato-DXd or osimertinib may be safe, tolerable, and/or effective in treating patients with metastatic EGFR-mutated non-small cell lung ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12775690/

Ivonescimab: promise or reality for advanced non-small cell ...

Ivonescimab: promise or reality for advanced non-small cell lung cancer? · Table 1. Summary of key efficacy outcomes of phase III trials KEYNOTE- ...

5.

smmttx.com

smmttx.com/news/press-releases/news-details/2025/Ivonescimab-Plus-Chemotherapy-Demonstrates-a-Statistically-Significant-Benefit-in-Overall-Survival-with-a-Hazard-Ratio-of-0-74-in-2L-Treatment-of-Patients-with-EGFRm-NSCLC-in-HARMONi-A-Study-Conducted-by-Akeso-in-China/default.aspx

Ivonescimab Plus Chemotherapy Demonstrates a ...

The safety profile demonstrated by ivonescimab in combination with chemotherapy, both in HARMONi-A and across the four positive Phase III study ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/41710928/

Efficacy and safety of ivonescimab in non-small cell lung ...

Efficacy and safety of ivonescimab in non-small cell lung cancer: a systematic review and meta-analysis of emerging clinical data · Abstract.

7.

frontiersin.org

frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1770637/full

Efficacy and safety of ivonescimab in non-small cell lung ...

Since the OS data of most studies are not yet mature, therefore, outcomes of interest included PFS, ORR, disease control rate (DCR), and the incidence of AEs.