SGN-MesoC2 for Solid Tumors

Recruiting at 17 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: Anticancer drugs, Radiotherapy

Disqualifiers: HIV, Uncontrolled hypertension, Diabetes, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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 blood. Once tumors have grown bigger in one place but haven't spread, they're called locally advanced. If your cancer has spread to other parts of your body, it's called metastatic. When a cancer has gotten so big it can't easily be removed or has spread to other parts of the body, it is called unresectable. These types of cancer are harder to treat. Patients in this study must have cancer that has come back or did not get better with treatment. Patients 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-08052666/SGN-MesoC2. PF-08052666/SGN-MesoC2 is a type of antibody-drug conjugate (ADC). ADCs are designed to stick to cancer cells and kill them. They may also stick to some normal cells. This study will have 3 parts. Part A and Part B of the study will find out how much PF-08052666/SGN-MesoC2 should be given to participants. Part C will use the information from Parts A and B to see if PF-08052666/SGN-MesoC2 is safe and if it works to treat solid tumor cancers.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anticancer therapy or focal radiotherapy at least 4 weeks before starting the study drug, or 2 weeks if your disease has progressed on treatment. The protocol does not specify other medications, so it's best to discuss your current medications with the trial team.

What makes the drug SGN-MesoC2 unique for treating solid tumors?

SGN-MesoC2 targets mesothelin, a protein often overexpressed in certain cancers like pancreatic and ovarian cancer, making it a promising option for tumors that express this protein. This drug is unique because it specifically targets cancer cells with high mesothelin expression, potentially reducing harm to normal tissues that have lower levels of this protein. ^{1 2 3 4 5}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults weighing at least 40 kg with certain advanced solid tumors, including ovarian cancer, NSCLC, pancreatic adenocarcinoma, colorectal cancer, and mesothelioma. Participants must have tried standard treatments without success or have no available standard options. They should be relatively active (ECOG score of 0 or 1) and have at least one measurable tumor lesion.

Inclusion Criteria

I have a tumor that can be measured using standard criteria.

I am fully active or can carry out light work.

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part A - Dose Finding

Determine the appropriate dose of PF-08052666/SGN-MesoC2 for participants

Up to 4 months

Part B - Dose Confirmation

Confirm the dose of PF-08052666/SGN-MesoC2 and assess safety

Up to 4 months

Part C - Efficacy Evaluation

Evaluate the safety and efficacy of PF-08052666/SGN-MesoC2 in treating solid tumor cancers

Approximately 1 year 4 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

30-37 days after the last dose

Treatment Details

Interventions

• SGN-MesoC2 (Monoclonal Antibodies)

Trial Overview SGN-MesoC2 is being tested in this study. It's an experimental antibody-drug conjugate designed to target and kill cancer cells while sparing normal ones. The trial has three parts: determining the right dose (Parts A & B) and assessing safety and effectiveness (Part C).

Participant Groups

Group I: PF-08052666 Experimental Treatment 1 Intervention

PF-08052666 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+

Findings from Research

The Tmod™ system, which combines a novel MSLN-activated CAR with an HLA-A*02-gated inhibitory receptor, allows for targeted killing of MSLN-positive cancer cells while protecting normal cells, reducing the risk of inflammation associated with MSLN-directed therapies.

In preclinical models, the Tmod system demonstrated comparable sensitivity to traditional MSLN CAR-T cells but with significantly improved safety, as it effectively spares normal cells even in mixed populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesothelin-specific CAR-T cell therapy that incorporates an HLA-gated safety mechanism selectively kills tumor cells. Tokatlian, T., Asuelime, GE., Mock, JY., et al.[2022]

A comprehensive analysis of 15,050 tumors revealed that mesothelin (MSLN) is expressed in 54% of tumor types, with particularly high levels in ovarian carcinomas (up to 97%) and pancreatic adenocarcinomas (up to 81%), suggesting these cancers could benefit from targeted therapies against MSLN.

While high MSLN expression is associated with advanced tumor stages and metastasis in colorectal adenocarcinomas, it does not correlate with malignancy in several other cancer types, indicating that while MSLN-targeted therapies may be promising, its prognostic value is limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,679 Tumors. Weidemann, S., Gagelmann, P., Gorbokon, N., et al.[2021]

HPN536 is a novel trispecific T-cell-activating protein that effectively targets mesothelin-expressing tumor cells, activating T cells to kill these cancer cells, demonstrating strong potency in preclinical models.

In nonhuman primates, HPN536 was well tolerated and showed a favorable pharmacokinetic profile, supporting its potential for weekly dosing in humans, and it is currently undergoing phase I clinical trials for patients with mesothelin-expressing cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Characterization of HPN536, a Trispecific, T-Cell-Activating Protein Construct for the Treatment of Mesothelin-Expressing Solid Tumors. Molloy, ME., Austin, RJ., Lemon, BD., et al.[2022]

Mesothelin (MSLN) was found to be highly expressed in 91.67% of pancreatic ductal adenocarcinoma (PDAC) cases studied, indicating its potential as a diagnostic and therapeutic target for this aggressive cancer.

The study showed no MSLN expression in para-cancerous tissues, suggesting that MSLN could help differentiate between cancerous and non-cancerous tissues, although its expression did not correlate with other clinicopathological factors like tumor size or stage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overexpression of Mesothelin in Pancreatic Ductal Adenocarcinoma (PDAC). Le, K., Wang, J., Zhang, T., et al.[2023]

The study involved 11 patients with pancreatic and ovarian cancers, using (89)Zr-PET imaging to assess the uptake of the mesothelin-targeting antibody MMOT0530A, which showed significant tumor uptake and distribution patterns.

The results indicated that the uptake of the tracer correlated with mesothelin expression in tumors, suggesting that (89)Zr-MMOT0530A-PET imaging could help tailor antibody-based treatments for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ImmunoPET with Anti-Mesothelin Antibody in Patients with Pancreatic and Ovarian Cancer before Anti-Mesothelin Antibody-Drug Conjugate Treatment. Lamberts, LE., Menke-van der Houven van Oordt, CW., ter Weele, EJ., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Mesothelin-specific CAR-T cell therapy that incorporates an HLA-gated safety mechanism selectively kills tumor cells. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Mesothelin Expression in Human Tumors: A Tissue Microarray Study on 12,679 Tumors. [2021]

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

Preclinical Characterization of HPN536, a Trispecific, T-Cell-Activating Protein Construct for the Treatment of Mesothelin-Expressing Solid Tumors. [2022]

4. Australia pubmed.ncbi.nlm.nih.gov

Overexpression of Mesothelin in Pancreatic Ductal Adenocarcinoma (PDAC). [2023]

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

ImmunoPET with Anti-Mesothelin Antibody in Patients with Pancreatic and Ovarian Cancer before Anti-Mesothelin Antibody-Drug Conjugate Treatment. [2021]