SGN-CEACAM5C for Advanced Cancers

Recruiting at19 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Seagen Inc.

Must not be taking: CEACAM5-targeted, ADC camptothecin

Disqualifiers: Other malignancy, Active cerebral disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called SGN-CEACAM5C for patients with hard-to-treat solid tumors that have either returned or didn't respond to standard treatments. The drug targets cancer cells and kills them. The study will determine the safe dosage and effectiveness of the drug.

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, you must have no appropriate standard therapy available at the time of enrollment, which might imply stopping certain treatments. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug SGN-CEACAM5C for advanced cancers?

Research shows that targeting CEACAM5, a protein often found in high amounts in certain cancers, with antibody-drug conjugates (ADCs) can effectively deliver cancer-killing agents to tumors. Studies on similar ADCs targeting CEACAM5 have demonstrated strong antitumor activity in various cancer cell lines and animal models, suggesting potential effectiveness for SGN-CEACAM5C. ^{1 2 3 4 5}

What safety data exists for SGN-CEACAM5C in humans?

In a study of tusamitamab ravtansine (SAR408701), an antibody-drug conjugate targeting CEACAM5, safety was evaluated in patients with advanced solid tumors. The study was a phase I trial, which is typically focused on assessing safety and determining appropriate dosage levels. ^{1 2 6 7 8}

What makes the drug SGN-CEACAM5C unique for treating advanced cancers?

SGN-CEACAM5C is unique because it targets the CEACAM5 protein, which is overexpressed in many cancers but not in normal tissues, allowing it to deliver a cytotoxic drug directly to cancer cells. This targeted approach aims to minimize damage to healthy cells and improve treatment effectiveness. ^{1 2 3 5 7}

Research Team

Medical Monitor

Principal Investigator

Seagen Inc.

Eligibility Criteria

This trial is for adults with advanced solid tumors that have returned, are resistant to treatment, or can't be removed by surgery. Participants must have specific types of cancer like colorectal, stomach, lung (non-small and small cell), or pancreatic cancer without standard treatment options available.

Inclusion Criteria

My cancer is confirmed to be advanced and cannot be removed by surgery.

My cancer is advanced, cannot be surgically removed, and has not responded to treatment.

My tumor can be biopsied, and I agree to the procedure.

Exclusion Criteria

I have been treated with a specific type of chemotherapy linked to an antibody.

I have been treated with drugs targeting CEACAM5 before.

My cancer has spread to my brain or its coverings.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part A)

Determine the appropriate dose of PF-08046050 for participants

8-12 weeks

Dose Expansion (Part B)

Further evaluate the safety and efficacy of PF-08046050 at the determined dose

12-16 weeks

Efficacy Evaluation (Part C)

Assess the safety and effectiveness of PF-08046050 in treating certain solid tumor cancers

16-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

30-37 days after last study treatment

Treatment Details

Interventions

• SGN-CEACAM5C (Monoclonal Antibodies)

Trial Overview SGN-CEACAM5C is being tested in this study. It's an experimental drug known as an antibody-drug conjugate designed to target and kill cancer cells. The trial has three parts: determining the right dosage (Parts A and B) and assessing safety and effectiveness at that dose (Part C).

Participant Groups

Group I: PF-08046050 Experimental Treatment 1 Intervention

PF-08046050 monotherapy

Who Is Running the Clinical Trial?

Seagen Inc.

Lead Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Findings from Research

The antibody-drug conjugate SAR408701 specifically targets CEACAM5, which is overexpressed in various cancers, and shows strong binding affinity to both human and cynomolgus monkey CEACAM5, indicating its potential for selective cancer therapy.

Preclinical studies demonstrated that SAR408701 effectively kills CEACAM5-expressing tumor cells and shows promising in vivo efficacy in mouse models, with a toxicity profile similar to that of the drug DM4 alone, suggesting a favorable safety profile for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Activity of SAR408701: A Novel Anti-CEACAM5-maytansinoid Antibody-drug Conjugate for the Treatment of CEACAM5-positive Epithelial Tumors. Decary, S., Berne, PF., Nicolazzi, C., et al.[2022]

The study developed a fully human single-domain antibody (UdAb) targeting CEACAM5, which is overexpressed in various cancers, and demonstrated its potential as an effective delivery system for the cytotoxic agent monomethyl auristatin E (MMAE).

The UdAb-MMAE conjugate showed strong antitumor efficacy in multiple cancer cell lines and significantly inhibited tumor growth in mouse models without causing significant weight loss, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel human single-domain antibody-drug conjugate targeting CEACAM5 exhibits potent in vitro and in vivo antitumor activity. Zhu, XY., Li, QX., Kong, Y., et al.[2023]

TAK-264, an investigational antibody-drug conjugate, demonstrated a manageable safety profile in adult patients with advanced gastrointestinal cancers, with the maximum tolerated dose established at 1.8 mg/kg and common side effects including nausea and neutropenia.

Preliminary results indicated potential antitumor activity, with one patient showing a partial response and three others achieving stable disease, suggesting that TAK-264 may be a promising treatment option for certain gastrointestinal malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of the Investigational Anti-Guanylyl Cyclase Antibody-Drug Conjugate TAK-264 (MLN0264) in Adult Patients with Advanced Gastrointestinal Malignancies. Almhanna, K., Kalebic, T., Cruz, C., et al.[2022]

A new conjugate combining a humanized anti-CEA single chain variable fragment (scFv) with mitomycin (MMC) was successfully created, showing strong immunoreactivity against colorectal cancer cells.

This conjugate effectively inhibited the growth of colorectal cancer cells and induced apoptosis in a concentration-dependent manner, suggesting its potential as a targeted therapy for colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Construction of humanized carcinoembryonic antigen specific single chain variable fragment and mitomycin conjugate. Chen, DJ., Tan, Z., Chen, F., et al.[2021]

The monoclonal antibody 6G5j effectively binds to multiple CEACAM proteins, which are important markers in colorectal cancer, enhancing the potential for improved detection of tumors and metastases.

In patient-derived orthotopic xenograft models, 6G5j conjugated with a near-infrared dye showed optimal imaging capabilities 48 hours post-injection, indicating its usefulness for fluorescence-guided surgery in colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-carcinoembryonic antigen-related cell adhesion molecule antibody for fluorescence visualization of primary colon cancer and metastases in patient-derived orthotopic xenograft mouse models. Hollandsworth, HM., Amirfakhri, S., Filemoni, F., et al.[2020]

In a phase I study involving 31 patients with solid tumors, tusamitamab ravtansine demonstrated a favorable safety profile, with reversible grade 3 microcystic keratopathy identified as the dose-limiting toxicity (DLT).

The maximum tolerated dose was established at 100 mg/m2, and the treatment showed preliminary antitumor activity, with three patients achieving confirmed partial responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and antitumor activity of the anti-CEACAM5-DM4 antibody-drug conjugate tusamitamab ravtansine (SAR408701) in patients with advanced solid tumors: first-in-human dose-escalation study. Gazzah, A., Bedard, PL., Hierro, C., et al.[2022]

Immunoconjugates combining vindesine with a monoclonal anti-CEA antibody showed effective tumor growth inhibition in mice with tumors expressing the CEA antigen, while having no effect on tumors that did not express this antigen.

The conjugated drug demonstrated lower toxicity compared to the free drug and maintained its efficacy for up to 5 months, suggesting a promising therapeutic approach for targeting specific tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and selectivity of vindesine monoclonal anti-carcinoembryonic antigen antibody conjugates on human tumor cell lines grown as xenografts in nude mice. Casson, AG., Ford, CH., Marsden, CH., et al.[2013]

References

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

Preclinical Activity of SAR408701: A Novel Anti-CEACAM5-maytansinoid Antibody-drug Conjugate for the Treatment of CEACAM5-positive Epithelial Tumors. [2022]

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

A novel human single-domain antibody-drug conjugate targeting CEACAM5 exhibits potent in vitro and in vivo antitumor activity. [2023]

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

Phase I Study of the Investigational Anti-Guanylyl Cyclase Antibody-Drug Conjugate TAK-264 (MLN0264) in Adult Patients with Advanced Gastrointestinal Malignancies. [2022]

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

Construction of humanized carcinoembryonic antigen specific single chain variable fragment and mitomycin conjugate. [2021]

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

Anti-carcinoembryonic antigen-related cell adhesion molecule antibody for fluorescence visualization of primary colon cancer and metastases in patient-derived orthotopic xenograft mouse models. [2020]

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

Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and antitumor activity of the anti-CEACAM5-DM4 antibody-drug conjugate tusamitamab ravtansine (SAR408701) in patients with advanced solid tumors: first-in-human dose-escalation study. [2022]

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

Efficacy and selectivity of vindesine monoclonal anti-carcinoembryonic antigen antibody conjugates on human tumor cell lines grown as xenografts in nude mice. [2013]