Ivonescimab + FOLFOX for Colorectal Cancer

((HARMONi-GI3) Trial)

Recruiting at 3 trial locations

Overseen By Nindhana Paranthaman, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Summit Therapeutics

Disqualifiers: MSI-H, BRAF V600E, GI obstruction, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a new drug, Ivonescimab, works with chemotherapy drugs for treating metastatic colorectal cancer (cancer that has spread beyond the colon). Researchers compare this treatment to a standard regimen involving Bevacizumab, another drug used with chemotherapy. The goal is to determine which approach better serves patients as a first treatment option. This trial seeks individuals diagnosed with metastatic colorectal cancer who have not yet received treatment and have at least one measurable tumor. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that ivonescimab is generally well-tolerated by patients with advanced solid tumors. When combined with FOLFOXIRI (a mix of chemotherapy drugs), ivonescimab presents a manageable safety profile for individuals with recurring or spreading colorectal cancer. While some patients might experience side effects, they are usually tolerable.

Bevacizumab, already approved by the FDA for other uses, has a well-known safety profile. It is often used with FOLFOX (another chemotherapy mix) for treating colorectal cancer. Although side effects can occur, they are typically known and monitored by doctors.

Both treatment options have undergone studies to ensure safety, though some side effects might occur. It is important to consult a healthcare professional about potential risks and benefits before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Ivonescimab combined with FOLFOX for colorectal cancer because it introduces a new active ingredient, Ivonescimab, which potentially enhances treatment effectiveness. Unlike traditional regimens that primarily rely on bevacizumab, Ivonescimab might offer an innovative mechanism of action, aiming to improve patient outcomes by working synergistically with chemotherapy. This novel combination approach has the potential to provide more durable responses and better manage the disease, making it a promising option in the fight against colorectal cancer.

What evidence suggests that this trial's treatments could be effective for metastatic colorectal cancer?

Research shows that ivonescimab holds promise in fighting colorectal cancer. In this trial, one group of participants will receive ivonescimab combined with mFOLFOX6. Earlier studies found that ivonescimab, when combined with chemotherapy, was effective, particularly for patients with certain genetic traits. Patients receiving ivonescimab experienced positive outcomes, such as tumor shrinkage. This treatment targets specific proteins that aid cancer growth, potentially slowing or stopping its spread. Although more information is needed, early results offer hope for treating advanced colorectal cancer. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for patients with metastatic colorectal cancer who haven't had systemic therapy for it. They should have a life expectancy of at least 6 months, one measurable lesion, and be fairly active (ECOG score 0 or 1). It's not for those with resectable disease, prior immunotherapy or anti-angiogenic treatment, inflammatory bowel diseases, certain genetic mutations (MSI-H/dMMR or BRAF V600E), GI obstruction signs, or recent ascites needing drainage.

Inclusion Criteria

Expected life expectancy ≥ 6 months

My colorectal cancer has spread and is confirmed by tests.

I have not had any treatment for my metastatic colorectal cancer.

Exclusion Criteria

My condition can be treated with surgery.

I have had immunotherapy or anti-angiogenic therapy for colorectal cancer.

I have or had inflammatory bowel disease like Crohn's or ulcerative colitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Ivonescimab or Bevacizumab in combination with mFOLFOX6 for up to 8 cycles

16 weeks

Bi-weekly visits for intravenous infusions

Maintenance Treatment

Participants receive maintenance treatment with Ivonescimab/Bevacizumab plus 5-Fluorouracil and Leucovorin

Up to 2 years

Bi-weekly visits for maintenance treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Ivonescimab

Trial Overview The study compares Ivonescimab combined with mFOLFOX6 chemotherapy to Bevacizumab combined with FOLFOX as first-line treatments in metastatic colorectal cancer. Participants are randomly assigned to either the new drug combo (Ivonescimab + chemo) or the known drug combo (Bevacizumab + chemo) in a double-blind setting where neither they nor the researchers know which group they're in.

How Is the Trial Designed?

Group I: Arm A: Ivonescimab in combination with mFOLFOX6 Experimental Treatment 1 Intervention

Subjects will receive Ivonescimab Plus mFOLFOX6 via intravenous infusion (IV) Q2W, up to 8 cycles. Afterward, Ivonescimab plus Leucovorin and 5-FU will be used for maintenance treatment (administered on Day 1 of each cycle, Q2W) up to 2 years.

Group II: Arm B: Bevacizumab in combination with mFOLFOX6 Active Control 1 Intervention

Subjects will receive bevacizumab Plus mFOLFOX6 (Oxaliplatin, Leucovorin and 5-Fluorouracil) via intravenous infusion (IV) Q2W, up to 8 cycles in treatment periods per the randomization schedule. Afterward, bevacizumab Plus 5-FU and Leucovorin will be used for maintenance treatment (administered on Day 1 of each cycle, Q2W) up to 2 years.

Who Is Running the Clinical Trial?

Summit Therapeutics

Lead Sponsor

Trials

18

Recruited

4,500+

Citations

1. akesobio.com akesobio.com/media/2300/ak112-crc.pdf

ak112-crc.pdf We report preliminary results from a phase 2 trial of ivonescimab and ligufalimab plus chemotherapy in patients with previously untreated ...

2. smmttx.com smmttx.com/pressrelease/promising-anti-tumor-activity-and-safety-of-ivonescimab-in-combination-therapies-in-crc-tnbc-and-hnscc-featured-at-esmo-2024-2/

Promising Anti-Tumor Activity and Safety of Ivonescimab in ... Two Oral Presentations Featured Updated Ivonescimab Data from Phase II Studies in CRC and TNBC in Addition to Poster Presentation on HNSCC

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

Phase 1a dose escalation study of ivonescimab (AK112/ ... Efficacy signals were also observed in patients with mismatch repair proficient (pMMR) colorectal cancer, non-small cell lung cancer, and both ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06959550

NCT06959550 | Phase II Study of Anti-PD-1/VEGF ... The goal of this clinical research study is to learn if ivonescimab can help to control previously treated, metastatic colorectal cancer.

5. fightcolorectalcancer.org fightcolorectalcancer.org/clinical-trial/nct05382442/

A Study of AK112 With or Without AK117 in Metastatic ... Trial in China, for patients with metastatic MSS only CRC. First part for patients receiving first line therapy for metastatic disease.

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02102-1/fulltext

514MO The efficacy and safety of ivonescimab with ... Ivonescimab with or without ligufalimab in combination with FOLFOXIRI showed promising efficacy and tolerable safety as 1L treatment in pts with mCRC. Clinical ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT07228832

Phase III Study of Ivonescimab or Bevacizumab Combined ... This trial will be performed as a phase 3, randomized, active-controlled, double-blind, multiregional study comparing Ivonescimab in combination ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11925807/

Safety, Pharmacokinetics, and Pharmacodynamics Evaluation ... We report the safety, pharmacokinetics (PK), and pharmacodynamics (PD) profiles of ivonescimab in patients suffered from advanced solid tumors.