Ivonescimab + Chemotherapy for Stomach Cancer

Overseen By Samuel Klempner, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: PD-1 inhibitors, PD-L1 inhibitors

Disqualifiers: Brain metastases, Hypertension, HIV, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment approach for individuals with stomach or esophagus cancer that has not spread, specifically targeting those with HER2-negative tumors. It combines ivonescimab, a novel drug, with the standard chemotherapy regimen FOLFOX. The trial aims to determine if this combination can effectively manage the disease. Individuals diagnosed with adenocarcinoma of the stomach or esophagus who have not yet received treatment for advanced disease may qualify for participation. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer care.

Do I have to stop taking my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are on certain treatments like corticosteroids or investigational agents, you may need to stop or adjust them. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that the combination of ivonescimab and FOLFOX chemotherapy is likely to be safe?

Studies have shown that ivonescimab, when combined with chemotherapy, generally has a manageable safety profile. In research involving patients with advanced stomach and gastroesophageal cancers, this combination was well-tolerated, with most side effects being mild and manageable. Although specific side effects were not listed, earlier studies suggest the treatment is promising in terms of both safety and effectiveness.

Since this trial is in an early stage, its main goal is to ensure the treatment's safety for participants. Early trials often focus on closely monitoring side effects. Previous research indicates that ivonescimab shows potential, with no unexpected safety concerns reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ivonescimab for stomach cancer because it introduces a novel approach by combining it with FOLFOX, a well-established chemotherapy regimen. Unlike standard treatments that primarily rely on chemotherapy alone, ivonescimab is a monoclonal antibody, potentially enhancing the immune system's ability to target cancer cells more precisely. This combination could offer improved efficacy by harnessing both the targeted action of ivonescimab and the broad-spectrum capabilities of FOLFOX. This dual-action strategy might enhance treatment outcomes and provide new hope for patients with stomach cancer.

What evidence suggests that ivonescimab plus chemotherapy might be an effective treatment for stomach cancer?

Research shows that ivonescimab, when combined with chemotherapy, yields promising results for treating advanced stomach cancer. In this trial, participants will receive ivonescimab with FOLFOX chemotherapy. Studies have found this combination safe and effective, with early results suggesting improved outcomes for patients with advanced stomach cancer. This treatment targets specific proteins that allow cancer cells to evade the immune system. Overall, evidence supports ivonescimab as a potential effective treatment option alongside standard chemotherapy for advanced stomach cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Samuel Klempner, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with advanced HER2-negative gastroesophageal cancer (GEA), which includes stomach and esophageal cancers. Participants should not have received first-line therapy yet. Specific eligibility details are not provided, but typically include factors like overall health status and no conflicting conditions.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document.

Participants must have disease that can be evaluated radiographically. This includes disease that may be measurable or non-measurable as per RECIST version 1.1.

The effects of ivonescimab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.

Exclusion Criteria

Participants with a documented history of impaired wound healing.

Participants who are receiving any other investigational agents for this condition are not eligible.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to ivonescimab.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Ivonescimab in combination with FOLFOX is administered every 2 weeks for up to 2 years, starting with ivonescimab alone in the first cycle.

Up to 2 years

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments continuing up to 90 days post-treatment.

90 days

Long-term follow-up

Participants are monitored for overall survival and progression-free survival for up to 5 years.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Ivonescimab

Trial Overview The study is testing the effectiveness of a new drug called Ivonescimab in combination with FOLFOX chemotherapy (which includes Oxaliplatin, Leucovorin, and 5-Fluorouracil) as a first-line treatment for patients with certain types of stomach and esophagus cancers.

How Is the Trial Designed?

Group I: Ivonescimab plus FOLFOX Experimental Treatment 4 Interventions

Ivonescimab will be given once every 2 weeks into your vein (by intravenous infusion) over about 60 minutes. For the first treatment ivonescimab will be given alone with no chemotherapy. FOLFOX is a combination of 5-fluorouracil, oxaliplatin, and leucovorin. Starting Cycle 2 on beyond FOLFOX will be given after ivonescimab once every 2 weeks into your vein (intravenously). Some may be given over a shorter period of time (as short as approximately 1 minute) and others up to approximately 120 minutes. Ivonescimab in combination with FOLFOX will be given for up to 2 years as long as no serious side effects and disease does not worsen.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Summit Therapeutics

Industry Sponsor

Trials

18

Recruited

4,500+

Citations

1. prnewswire.com prnewswire.com/news-releases/ivonescimab-harmoni-6-results-selected-for-esmo-2025-lba-final-phase-iii-results-of-cadonilimab-as-first-line-therapy-for-advanced-gastric-cancer-to-be-published-as-an-oral-presentation-302563756.html

Ivonescimab HARMONi-6 Results Selected for ESMO 2025 ... Cadonilimab is a first-in-class bispecific antibody targeting PD-1 and CTLA-4 developed by Akeso that is currently approved for first line ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e16037

Cadonilimab in combination with ivonescimab and ... AK104 combined with AK112 and chemo as 1L treatment showed a promising tolerable safety profile and highly encouraging efficacy in pts with advanced G/GEJA.

3. 1stoncology.com 1stoncology.com/blog/ivonescimab-harmoni-6-results-selected-for-esmo-2025-lba-final-phase-iii-results-of-cadonilimab-as-first-line-therapy-for-advanced-gastric-cancer-to-be-published-as-an-oral-presentation1234656155/

Ivonescimab HARMONi-6 Results Selected for ESMO 2025 ... This study, which evaluates ivonescimab in combination with chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for ...

4. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/579135

Testing Ivonescimab in Combination With Chemotherapy in ... The goal of this clinical trial is to evaluate the addition of ivonescimab to standard chemotherapy in patients with advanced or metastatic gastric and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06814158

Study Details | NCT06814158 | Neoadjuvant Ivonescimab ... The combination of neoadjuvant chemotherapy and immunotherapy significantly improved the perioperative outcomes of ESCC patients, and the safety and efficacy of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06904300

NCT06904300 | Ivonescimab (AK112) Plus Paclitaxel as ... This is a randomized, controlled, multi-center Phase II trial (N ≈ 110) conducted in China to assess the safety and antitumor activity of AK112 combined ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT447150

The safety and efficacy of ivonescimab in combination ... Ivonescimab combined with chemotherapy as 1L treatment demonstrated promising efficacy in pts with advanced BTC.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11033648/

Phase 1a dose escalation study of ivonescimab (AK112/ ... This study supports that ivonescimab has manageable safety profiles, promising efficacy signals. Several studies with ivonescimab monotherapy or ...

9. cancer.gov cancer.gov/clinicaltrials/NCI-2025-07695

Ivonescimab in Combination with a Standard ... Leucovorin is a form of folic acid. It can enhance the effectiveness of fluorouracil and protect healthy cells from the toxic effects of chemotherapy drugs.