Sotevtamab + FOLFOX for Colorectal Cancer

(EGIA-003 Trial)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Alethia Biotherapeutics

Must not be taking: Anti-VGFR, Anti-EGFR, Anti-VEGF, Immunosuppressants

Disqualifiers: MMR-deficient tumor, Hereditary cancer, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, Sotevtamab, combined with standard chemotherapy in colorectal cancer patients whose cancer has spread mainly to the liver. The goal is to shrink the tumors before surgery to make them easier to remove.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain cancer treatments or high doses of steroids while participating. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Sotevtamab + FOLFOX for colorectal cancer?

Research shows that combination therapies like FOLFOX, which includes drugs like oxaliplatin and fluorouracil, have improved response rates and survival in colorectal cancer patients. Additionally, monoclonal antibodies, similar to Sotevtamab, have shown potential in extending survival when added to chemotherapy regimens. ^{1 2 3 4 5}

Is the combination of Sotevtamab and FOLFOX safe for humans?

The FOLFOX regimen, which includes oxaliplatin and 5-fluorouracil, is generally well tolerated, but known side effects can include low blood cell counts, nausea, vomiting, nerve damage, and rarely, lung issues. There is no specific safety data available for Sotevtamab in combination with FOLFOX, but FOLFOX itself has been used safely in various cancer treatments. ^{6 7 8 9 10}

What makes the drug Sotevtamab + FOLFOX unique for colorectal cancer?

Sotevtamab + FOLFOX is unique because it combines a novel monoclonal antibody, Sotevtamab, with the established FOLFOX chemotherapy regimen, which includes oxaliplatin, fluorouracil, and folinic acid. This combination aims to enhance the treatment's effectiveness by targeting specific cancer cell pathways, potentially offering a new option for patients with colorectal cancer. ^{1 3 7 11 12}

Research Team

Eligibility Criteria

This trial is for colorectal cancer patients with liver metastases. Participants must be eligible for surgery to remove these metastases and have not yet had any treatment specifically targeting the liver tumors.

Inclusion Criteria

I am 18 years or older and can sign the consent form.

I can take care of myself but might not be able to do heavy physical work.

Participants must have given written personally signed and dated informed consent to participate in the trial in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines, before completing any trial related procedures.

Exclusion Criteria

Participants with a known history of human immunodeficiency (HIV).

I have a genetic form of colorectal cancer.

Participants who are currently participating or have participated in a trial of an investigational agent or using an investigational device within 21 days of the first dose of trial treatment. The 21-day window should be calculated using the last dose of an investigational agent or last use of an investigational device.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Sotevtamab at 800 mg once weekly for 6 cycles combined with FOLFOX once every 2 weeks for the first 4 cycles

12 weeks

Weekly visits for Sotevtamab, bi-weekly visits for FOLFOX

Surgery

Participants undergo liver metastasis resection with or without primary cancer resection following recovery from preoperative neoadjuvant systemic chemotherapy

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including evaluation of treatment-emergent adverse events and pathological response

4-6 weeks

Treatment Details

Interventions

• FOLFOX (Chemotherapy)
• Sotevtamab (Monoclonal Antibodies)

Trial Overview The study tests Sotevtamab, given weekly, combined with FOLFOX chemotherapy every two weeks. This regimen is followed for six cycles before surgical removal of the liver metastases.

Participant Groups

Group I: Sotevtamab and FOLFOX Experimental Treatment 2 Interventions

Sotevtamab at 800 mg IV infusion once weekly on Days 1 and 8 for 6 cycles combined with FOLFOX (oxaliplatin 85 mg/m² IV infusion + leucovorin 400 mg/m² IV infusion + 5-Fluorouracil (5-FU) 400 mg/m² IV bolus + 5-FU 2400 mg/m² continuous IV infusion over 46 hours) once every 2 weeks on Day 1 for the first 4 cycles.

Who Is Running the Clinical Trial?

Alethia Biotherapeutics

Lead Sponsor

Trials

3

Recruited

70+

Findings from Research

Combination therapy using irinotecan or oxaliplatin with infusional 5-FU and folinic acid has increased response rates to about 50% and extended median overall survival to 20 months in patients with metastatic colorectal cancer.

Monoclonal antibodies like bevacizumab and cetuximab have shown to significantly enhance treatment outcomes, with bevacizumab extending survival by over 4 months compared to chemotherapy alone, and cetuximab being effective after progression with irinotecan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[New therapy options in colorectal carcinoma]. Folprecht, G., Köhne, CH.[2018]

In a phase II trial involving 31 patients with metastatic colorectal cancer, the combination of FOLFOX, bevacizumab, and cetuximab achieved a 55% objective response rate and a median overall survival of 25.7 months, indicating promising efficacy.

The treatment regimen was generally well-tolerated, although significant side effects were observed, including neutropenia and rash; the role of cetuximab in enhancing efficacy remains uncertain and should be further evaluated with K-RAS testing in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of FOLFOX6, bevacizumab, and cetuximab in the first-line treatment of metastatic colorectal cancer. Spigel, DR., Greco, FA., Waterhouse, D., et al.[2015]

In patients with inoperable or metastatic colorectal cancer, initial treatment with single-agent fluorouracil (or capecitabine) is recommended over combination therapies when the disease is unlikely to become operable, as it does not shorten overall survival compared to combination regimens.

The addition of monoclonal antibodies like cetuximab and panitumumab in first-line treatment has not shown a significant improvement in overall survival, suggesting their use should be reconsidered, particularly in patients with KRAS mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of metastatic colorectal cancer. [2013]

In a study of 154 patients with metastatic colorectal carcinoma (mCRC), the combination of panitumumab and FOLFIRI showed a higher objective response rate (ORR) in patients with RAS wild type (WT) tumors (59%) compared to those with RAS mutant (MT) tumors (41%).

The treatment was well tolerated, with no new safety concerns, and patients with RAS WT tumors experienced longer median response durations (13.0 months) and progression-free survival (11.2 months) compared to those with RAS MT tumors (5.8 months and 7.3 months, respectively).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of tumour RAS/BRAF status in a first-line study of panitumumab + FOLFIRI in patients with metastatic colorectal cancer. Karthaus, M., Hofheinz, RD., Mineur, L., et al.[2018]

Panitumumab has shown promising antitumor activity in metastatic colorectal cancer, achieving a 10% response rate as a standalone treatment and a 36% response rate when combined with chemotherapy, based on phase II studies.

In a phase III study, panitumumab demonstrated a significant clinical advantage over best supportive care as a third-line monotherapy, and it has a good tolerability profile with no maximum tolerated dose established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab: the evidence of its therapeutic potential in metastatic colorectal cancer care. Martinelli, E., Morgillo, F., Troiani, T., et al.[2021]

In a real-world study of 362 patients with metastatic colorectal cancer treated with ramucirumab + FOLFIRI, 84.3% experienced adverse events, with common issues including decreased neutrophil count, hypertension, and diarrhea, indicating that while the treatment is effective, it does carry a significant risk of side effects.

The 12-month survival rate for patients on the ramucirumab + FOLFIRI regimen was 59%, with most mortality attributed to disease progression rather than treatment-related complications, suggesting that the regimen is manageable and aligns with previous clinical trial safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing safety study of ramucirumab with FOLFIRI in patients with metastatic colorectal cancer. Masuishi, T., Nagaoka, S., Jin, L., et al.[2022]

In a phase Ib study involving 6 Japanese patients with metastatic colorectal carcinoma, the combination of ramucirumab and FOLFIRI was found to be well-tolerated, with only one patient experiencing a dose-limiting toxicity.

While all patients had at least one grade 3 or higher adverse event, there were no serious adverse events or deaths, suggesting that this treatment combination is relatively safe for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of Second-line Ramucirumab plus FOLFIRI in Japanese Patients with Metastatic Colorectal Carcinoma. Yoshino, T., Yamazaki, K., Gotoh, M., et al.[2023]

The TRIPLETE study is a phase III trial comparing two chemotherapy regimens (mFOLFOX6 and modified FOLFOXIRI) combined with panitumumab in patients with RAS and BRAF wild-type metastatic colorectal cancer, aiming to determine which regimen provides a better overall response rate.

This study is significant as it seeks to clarify the effectiveness of intensified chemotherapy in combination with anti-EGFR therapy, addressing a gap in knowledge regarding treatment options for this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TRIPLETE: a randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer. Borelli, B., Moretto, R., Lonardi, S., et al.[2022]

A 66-year-old male with metastatic rectal adenocarcinoma developed acute pulmonary fibrosis after 12 cycles of chemotherapy with oxaliplatin and 5-FU/folinic acid, highlighting a rare but serious side effect of this treatment regimen.

Despite the regimen being generally well tolerated, this case emphasizes the need for clinicians to consider pulmonary toxicity early when patients present with unexplained pulmonary infiltrates, as timely recognition may improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary fibrosis after chemotherapy with oxaliplatin and 5-fluorouracil for colorectal cancer. Mundt, P., Mochmann, HC., Ebhardt, H., et al.[2022]

In a study of 66 patients with chemotherapy-refractory metastatic colorectal cancer, the combination of cetuximab with bevacizumab and mFOLFOX6 showed manageable safety, but significant toxicity led to a high discontinuation rate, with 56% of patients stopping treatment before disease progression.

Despite not causing excessive life-threatening toxicity, the addition of cetuximab resulted in a notable number of patients experiencing severe side effects, prompting the conclusion that this combination therapy should not be used together for treating metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab is associated with excessive toxicity when combined with bevacizumab Plus mFOLFOX6 in metastatic colorectal carcinoma. Ocean, AJ., Polite, B., Christos, P., et al.[2021]

In a study of 65 patients with KRAS wild-type metastatic colorectal cancer who were resistant to standard chemotherapy, the combination of panitumumab and irinotecan resulted in an objective response rate of 29.2%, with a median overall survival of 9.7 months.

The treatment was particularly effective in patients without additional mutations, showing a 46.3% response rate, while those with other mutations (NRAS, BRAF, or rare KRAS) did not respond, highlighting the importance of biomarker selection in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab combined with irinotecan for patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy: a GERCOR efficacy, tolerance, and translational molecular study. André, T., Blons, H., Mabro, M., et al.[2023]

In a meta-analysis of four randomized controlled trials involving 1270 patients with metastatic colorectal cancer, adding cetuximab or panitumumab to oxaliplatin-based chemotherapy did not significantly improve overall survival or progression-free survival for KRAS wild type patients.

The combination therapy did not enhance the overall response rate compared to chemotherapy alone, and while there was a slight increase in toxicities with anti-EGFR drugs, the overall efficacy of the treatment remained unchanged.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No survival benefit from adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first-line treatment of metastatic colorectal cancer in KRAS wild type patients: a meta-analysis. Zhou, SW., Huang, YY., Wei, Y., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

[New therapy options in colorectal carcinoma]. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of FOLFOX6, bevacizumab, and cetuximab in the first-line treatment of metastatic colorectal cancer. [2015]

3. France pubmed.ncbi.nlm.nih.gov

Chemotherapy of metastatic colorectal cancer. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Impact of tumour RAS/BRAF status in a first-line study of panitumumab + FOLFIRI in patients with metastatic colorectal cancer. [2018]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Panitumumab: the evidence of its therapeutic potential in metastatic colorectal cancer care. [2021]

6. China pubmed.ncbi.nlm.nih.gov

A post-marketing safety study of ramucirumab with FOLFIRI in patients with metastatic colorectal cancer. [2022]

7. Greece pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of Second-line Ramucirumab plus FOLFIRI in Japanese Patients with Metastatic Colorectal Carcinoma. [2023]

8. England pubmed.ncbi.nlm.nih.gov

TRIPLETE: a randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Pulmonary fibrosis after chemotherapy with oxaliplatin and 5-fluorouracil for colorectal cancer. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Cetuximab is associated with excessive toxicity when combined with bevacizumab Plus mFOLFOX6 in metastatic colorectal carcinoma. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Panitumumab combined with irinotecan for patients with KRAS wild-type metastatic colorectal cancer refractory to standard chemotherapy: a GERCOR efficacy, tolerance, and translational molecular study. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

No survival benefit from adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first-line treatment of metastatic colorectal cancer in KRAS wild type patients: a meta-analysis. [2023]