SGN-CEACAM5C for Advanced Cancers

Recruiting at 45 trial locations

Overseen By Marwan G Fakih

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Seagen Inc.

Must not be taking: CEACAM5-targeted, ADC camptothecin

Disqualifiers: Other malignancy, Active cerebral disease, others

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

Compensation: Varies

Number of Visits: Unknown

494 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PF-08046050 (also known as SGN-CEACAM5C, an anti-CEACAM 5 antibody drug conjugate) for individuals with certain advanced and hard-to-treat solid tumors, such as those in the lungs, liver, or colon, that have not responded to other treatments. The trial aims to assess the safety and effectiveness of this drug, both alone and in combination with another drug, bevacizumab. It is open to participants whose cancer has returned or continued to grow after standard treatments. Participants must have specific types of cancer, such as colorectal or non-small cell lung cancer, and their cancer must be inoperable or have metastasized. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Research shows that PF-08046050, the treatment being tested, is an antibody-drug conjugate (ADC). ADCs target and kill cancer cells but might also affect some healthy cells. This treatment targets solid tumors that are difficult to treat or have spread.

Researchers are testing the safety of PF-08046050 in different ways: using it alone and in combination with bevacizumab, a drug that helps stop tumors from growing by preventing new blood vessels from forming. Ongoing studies aim to assess how well patients tolerate these treatments and monitor any side effects.

As a Phase 1 trial, the primary focus is on safety. Early-stage trials like this involve close monitoring to identify side effects and determine the best dose. Specific safety data from these studies is not yet available, but the trial phase indicates that researchers are carefully evaluating the treatment to ensure it is safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SGN-CEACAM5C for advanced cancers because it offers a fresh approach compared to current treatments like chemotherapy and targeted therapies. SGN-CEACAM5C specifically targets the CEACAM5 protein, which is often found on cancer cells, potentially leading to more precise attacks on tumors with less damage to healthy cells. This targeted action could mean fewer side effects and improved effectiveness against certain advanced cancers. Additionally, the combination of PF-08046050 with bevacizumab aims to enhance the anti-tumor effects by disrupting blood supply to the tumor while targeting the cancer cells directly.

What evidence suggests that this trial's treatments could be effective for advanced cancers?

Research shows that drugs like PF-08046050, known as antibody-drug conjugates (ADCs), hold promise because they can target and kill cancer cells while sparing normal cells. This trial will study PF-08046050 as a monotherapy in one arm, targeting a protein called CEACAM5, often found on hard-to-treat solid tumors. Early results suggest this method can work, but researchers are still studying its safety and efficacy. Another arm of this trial will evaluate PF-08046050 in combination with bevacizumab, a drug that cuts off the blood supply to tumors, to assess its potential for enhanced effectiveness. Detailed results on the effectiveness of this combination are not yet available. These factors make PF-08046050 a hopeful option for treating difficult cancers. ^{1 2 3 4 6}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• SGN-CEACAM5C

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).

How Is the Trial Designed?

Group I: PF-08046050 +bevacizumab Experimental Treatment 2 Interventions

PF-08046050 combination with bevacizumab

Group II: 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

Seagen, a wholly owned subsidiary of Pfizer

Lead Sponsor

Trials

20

Recruited

4,900+

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

SGN-35, an antibody-drug conjugate targeting CD30, effectively releases the potent drug MMAE inside CD30(+) cancer cells, achieving high intracellular concentrations that contribute to its therapeutic effects.

MMAE not only kills CD30(+) cells but can also diffuse to and exert cytotoxic effects on neighboring CD30(-) cells, enhancing the overall antitumor activity of SGN-35 in mixed tumor environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Okeley, NM., Miyamoto, JB., Zhang, X., et al.[2021]

Citations

1. pfizerclinicaltrials.com pfizerclinicaltrials.com/find-a-trial/nct06131840-colorectal-neoplasms-trial

A Study of SGN-CEACAM5C in Adults With Advanced ... This study will test the safety of PF-08046050 in participants with solid tumors that are hard to treat or have spread throughout the body.

2. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/438555

A Study of SGN-CEACAM5C in Adults With Advanced ... Participants must have a solid tumor cancer that can't be treated with standard of care drugs. This clinical trial uses an experimental drug called PF-08046050.

3. npcf.us npcf.us/clinical-trials/a-study-of-sgn-ceacam5c-in-adults-with-advanced-solid-tumors/

A Study Of SGN-CEACAM5C In Adults With Advanced ... This clinical trial is studying advanced solid tumors. Solid tumors are cancers that start in a part of your body like your lungs or liver instead of your ...

4. theglobeandmail.com theglobeandmail.com/investing/markets/stocks/SNY/pressreleases/34204579/sanofis-latest-clinical-trial-a-new-hope-for-advanced-solid-tumors/

Sanofi's Latest Clinical Trial: A New Hope for Advanced ... ... Advanced Solid Tumors aims to evaluate the safety and efficacy of the experimental drug PF-08046050 in treating advanced solid tumors. These ...

5. withpower.com withpower.com/trial/phase-1-carcinoma-11-2023-2ac38

SGN-CEACAM5C for Advanced Cancers 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 ...

6. researchstudies.cuanschutz.edu researchstudies.cuanschutz.edu/Study/23-2329

Find a Research Study PF-08046050 is a type of antibody-drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them. They may also stick to some normal cells.