Ivonescimab for Colorectal Cancer

Overseen By Saurav Haldar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must be taking: PD-1/PD-L1 inhibitors

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Cardiac impairment, Hypertension, Autoimmune, 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: 1 year

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ivonescimab, an experimental drug, to determine its effectiveness in controlling colorectal cancer that has spread and hasn't responded to previous treatments. It seeks participants with advanced colorectal cancer who have specific tumor characteristics and have undergone certain cancer therapies. Those with metastatic colorectal cancer who have experienced progression after specific immune therapies may find this trial suitable. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that systemic anti-cancer treatment should not be taken within 14 days before starting the study treatment. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that ivonescimab is likely to be safe for humans?

Research has shown that ivonescimab is generally safe for people with colorectal cancer. Studies have found that ivonescimab, whether used alone or with other treatments, is usually well-tolerated. Common side effects include tiredness, nausea, and diarrhea, but these are mostly mild to moderate. This suggests that ivonescimab could be a safe option for treating colorectal cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for colorectal cancer, which often include chemotherapy and radiation targeting rapidly dividing cells, Ivonescimab works through a unique mechanism by targeting specific cancer pathways more precisely. Researchers are excited about Ivonescimab because it is an innovative antibody-drug conjugate that combines precision targeting with the cancer-killing power of chemotherapy, potentially leading to better outcomes with fewer side effects. This targeted approach could improve the quality of life for patients by reducing damage to healthy cells and offering a more personalized treatment option.

What evidence suggests that ivonescimab might be an effective treatment for colorectal cancer?

Research shows that ivonescimab holds promise in managing advanced colorectal cancer. In this trial, participants will receive ivonescimab as a standalone treatment. Studies indicate that combining ivonescimab with treatments like FOLFOXIRI (a type of chemotherapy) can enhance its tumor-fighting ability. One study showed that patients experienced better disease control, suggesting that ivonescimab may help slow cancer growth. Additionally, the treatment is generally safe and well-tolerated. These findings suggest that ivonescimab could be an effective option for managing previously treated colorectal cancer. ^{1 3 4 6 7}

Who Is on the Research Team?

Saurav Haldar, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with metastatic colorectal cancer that has worsened after treatment, including anti-PD-1/PD-L1 therapy. Participants must have measurable disease, a life expectancy over 3 months, and be able to provide recent tumor tissue. They should not have severe allergies or conditions that could affect study participation.

Inclusion Criteria

My cancer is an advanced type that started in my colon or rectum.

My cancer progressed after treatment with specific immune therapies.

I can provide a recent sample of my tumor for testing.

Exclusion Criteria

My tumor is affecting nearby major organs or blood vessels.

I have not had cancer treatment within the specified time.

I have not had a severe COPD flare-up in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ivonescimab to evaluate its efficacy and safety in metastatic colorectal cancer

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ivonescimab

Trial Overview The trial is testing Ivonescimab's effectiveness in controlling metastatic colorectal cancer after previous treatments failed. It involves patients who've progressed on immune checkpoint inhibitors and requires them to have specific genetic markers of their tumors tested.

How Is the Trial Designed?

Group I: Treatment with Ivonescimab Experimental Treatment 1 Intervention

Participants will be assigned to the study using a Bayesian Optimal Phase 2 (BOP2) design

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Summit Therapeutics

Industry Sponsor

Trials

18

Recruited

4,500+

Akesobio Australia Pty Ltd

Industry Sponsor

Trials

10

Recruited

690+

Summit Therapeutics Sub, Inc

Collaborator

Trials

1

Recruited

50+

Published Research Related to This Trial

New agents like irinotecan (CPT-11) and oxaliplatin have shown promising efficacy in treating colorectal carcinoma (CRC), especially for patients resistant to standard therapies like 5-fluorouracil (5-FU) and leucovorin.

Combination therapies involving 5-FU with newer agents such as trimetrexate, capecitabine, and S-1 are showing encouraging response rates, suggesting potential changes in the standard treatment protocols for advanced CRC in the near future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New drugs in the treatment of colorectal carcinoma. Punt, CJ.[2019]

Cetuximab combined with chemotherapy shows a good overall response rate (43.1%) and overall survival (28.5 months) in patients with advanced colorectal cancer and unclear K-ras status, based on a study of 102 patients.

The treatment is considered safe, with common side effects including acneiform eruptions and neutropenia, but no treatment-related deaths were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of cetuximab combined with chemotherapy for patients with advanced colorectal cancer and unclear K-ras status]. Guo, GF., Xia, LP., Qiu, HJ., et al.[2018]

In a phase II trial involving 82 patients with advanced colorectal cancer, the combination of cetuximab and FOLFOX6 showed an overall response rate of 44.8%, indicating its efficacy as a first-line treatment.

Patients who developed skin toxicity while on the treatment had significantly longer median survival times (21.7 months) compared to those who did not experience this side effect, suggesting a potential correlation between skin reactions and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial of FOLFOX6 and cetuximab in the first-line treatment of patients with metastatic colorectal cancer. Boccia, RV., Cosgriff, TM., Headley, DL., et al.[2016]

In a phase II study involving 99 patients with wild-type KRAS colorectal cancer, the biweekly combination of cetuximab and FOLFOX-4 achieved an overall response rate (ORR) of 60.6%, indicating significant efficacy as a first-line treatment.

The safety profile was consistent with previous studies, with common grade 3-4 toxicities including neutropenia (32.3%) and acne-like rash (15.2%), suggesting that the biweekly regimen is both effective and manageable for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biweekly cetuximab in combination with FOLFOX-4 in the first-line treatment of wild-type KRAS metastatic colorectal cancer: final results of a phase II, open-label, clinical trial (OPTIMIX-ACROSS Study). Fernandez-Plana, J., Pericay, C., Quintero, G., et al.[2023]

Citations

1. 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

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

514MO The efficacy and safety of ivonescimab with ... This study aimed to evaluate the efficacy and safety of ivonescimab with or without ligufalimab in combination with FOLFOXIRI in mCRC.

3. akesobio.com akesobio.com/en/media/akeso-news/240918/

Akeso Published First-Ever Efficacy Data for PD-1/VEGF ... As of February 29, 2024, the median follow-up time for the ivonescimab plus ligufalimab combination with FOLFOXIRI group was 9.6 months, and 9.0 ...

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. firstwordpharma.com firstwordpharma.com/story/6323677

Summit Therapeutics Announces Expansion of ... Summit Therapeutics Announces Expansion of Ivonescimab Global Phase III Development Program with HARMONi-GI3 Study in 1L Colorectal Cancer.

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

ak112-crc.pdf • Ivonescimab +/- ligufalimab in combination with FOLFOXIRI showed manageable safety profile in recurrent or metastatic CRC. − The most ...

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

Ivonescimab: Novel Bispecific Antibody Targeting PD-1 & VEGF We report the safety, pharmacokinetics (PK), and pharmacodynamics (PD) profiles of ivonescimab in patients suffered from advanced solid tumors.