SGN-EGFRd2 for Advanced Cancer

Recruiting at32 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Must not be taking: Aminobisphosphonates

Disqualifiers: Active CNS metastases, Recent thromboembolism, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This study will test the safety of a drug called PF-08046052/SGN-EGFRd2 in participants with advanced solid tumors. It will also study the side effects of this drug. A side effect is anything a drug does to the body besides treating the disease. Participants will have cancer that cannot be removed (unresectable) or has spread through the body (metastatic). This study will have three parts. Parts A and B of the study will find out how much PF-08046052/SGN-EGFRd2 should be given to participants. Part C will use the dose found in parts A and B to find out how safe PF-08046052/SGN-EGFRd2 is and if it works to treat solid tumor cancers.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot have received aminobisphosphonate IV treatments within 4 weeks of starting the study drug.

What data supports the effectiveness of the drug SGN-EGFRd2 for advanced cancer?

The research on similar treatments, like erlotinib combined with other drugs, shows some effectiveness in treating advanced non-small-cell lung cancer (NSCLC). This suggests that drugs targeting similar pathways, like SGN-EGFRd2, might also be effective for certain advanced cancers. ^{1 2 3 4 5}

What makes the drug SGN-EGFRd2 unique for treating advanced cancer?

SGN-EGFRd2 is unique because it targets the epidermal growth factor receptor (EGFR), which is often amplified in certain cancers, potentially offering a more tailored approach for patients with EGFR-amplified tumors. This drug may provide an alternative for patients who have not responded to other treatments, especially in cases where EGFR amplification is a key factor in the cancer's progression. ^{4 6 7 8 9}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults with advanced solid tumors like colorectal, non-small cell lung, or squamous cell cancers that have spread and can't be removed. They should have tried other treatments without success or cannot tolerate them. Participants need to be in good physical condition (ECOG score of 0 or 1) and must not have had certain serious blood clots or another cancer within the last three years.

Inclusion Criteria

For Part C, you must have a specific type of cancer that has come back, not responded to treatment, or you cannot tolerate standard treatments. You should have a good level of physical function and have a tumor that can be measured.

My cancer has returned, is not responding, or I can't tolerate standard treatments. It's one of CRC, NSCLC, or HNSCC and cannot be surgically removed.

My cancer has returned, is not responding, or I can't tolerate standard treatments, and there are no suitable standard treatments available.

Exclusion Criteria

I have had a blood clot or stroke in the last 6 months, am on blood thinners, or can't take blood clot prevention medication.

I have stable brain metastases and haven't taken steroids for them in the last 7 days.

I haven't had any other cancers in the last 3 years, or if I did, they were not serious.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part A and B)

Determine the appropriate dose of PF-08046052/SGN-EGFRd2 for participants

12-16 weeks

Dose Expansion (Part C)

Evaluate the safety and efficacy of the determined dose in treating solid tumor cancers

24-48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Treatment Details

Interventions

• SGN-EGFRd2 (Monoclonal Antibodies)

Trial Overview SGN-EGFRd2 is being tested for safety and effectiveness in treating advanced solid tumors. The study has three parts: determining the right dose (Parts A & B) and then assessing its safety at that dose while checking if it helps treat these cancers (Part C).

Participant Groups

Group I: PF-08046052/SGN-EGFRd2 Experimental Treatment 1 Intervention

PF-08046052/SGN-EGFRd2 monotherapy

Who Is Running the Clinical Trial?

Seagen, a wholly owned subsidiary of Pfizer

Lead Sponsor

Trials

20

Recruited

4,900+

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

Findings from Research

In a review of five clinical trials involving 1970 patients, second-line PD-1 inhibitors significantly improved overall survival (OS) and objective response rate (ORR) in advanced esophageal squamous cell carcinoma (ESCC) compared to conventional chemotherapy, particularly in patients with positive PD-L1 status.

PD-1 inhibitors also demonstrated a better safety profile, with lower incidences of severe treatment-related adverse events (TRAEs) compared to chemotherapy, although they did not show significant improvements in progression-free survival (PFS) or disease control rate (DCR).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 inhibitors versus chemotherapy as second-line treatment for advanced esophageal squamous cell carcinoma: a meta-analysis. Zhu, X., Shanzhou, Q., Li, D., et al.[2022]

The combination of nivolumab and erlotinib was found to be tolerable in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC), with treatment-related grade 3 toxicities occurring in only five out of twenty patients, and no severe grade 4 toxicities reported.

Among the TKI-treated patients, the objective response rate was 15%, with some patients experiencing durable responses lasting up to 38.2 months, indicating potential efficacy of this combination therapy in managing advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC. Gettinger, S., Hellmann, MD., Chow, LQM., et al.[2019]

In a phase II trial involving 103 patients with advanced non-squamous NSCLC, the combination of bevacizumab and erlotinib achieved a disease stabilization rate of 54.5% after 12 weeks, indicating significant efficacy in managing the disease.

The treatment was well-tolerated with no unexpected toxicities, and the median overall survival was 14.1 months, comparable to standard chemotherapy, suggesting that this combination therapy is a viable first-line option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and erlotinib (BE) first-line therapy in advanced non-squamous non-small-cell lung cancer (NSCLC) (stage IIIB/IV) followed by platinum-based chemotherapy (CT) at disease progression: a multicenter phase II trial (SAKK 19/05). Zappa, F., Droege, C., Betticher, D., et al.[2018]

In a study of 6,667 advanced gastroesophageal adenocarcinoma (GEA) tissue specimens, 4.0% were found to have FGFR2 alterations, with the majority being FGFR2 amplifications, indicating a potential target for therapy in this cancer type.

Approximately 20% of FGFR2-altered cases also had concurrent alterations in other receptor tyrosine kinases and oncogenes, suggesting that comprehensive genomic profiling is essential for optimizing treatment strategies and patient selection for clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FGFR2-Altered Gastroesophageal Adenocarcinomas Are an Uncommon Clinicopathologic Entity with a Distinct Genomic Landscape. Klempner, SJ., Madison, R., Pujara, V., et al.[2020]

Nintedanib, a drug targeting multiple receptor tyrosine kinases, achieved modest disease stabilization in 19% of patients with metastatic esophagogastric cancer, with 6 out of 32 patients remaining progression-free at 6 months.

The treatment was well tolerated, with few severe side effects, although alterations in cell-cycle pathway genes were linked to poorer outcomes, suggesting they may serve as important biomarkers for predicting response to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Combined VEGFR1-3, PDGFα/β, and FGFR1-3 Blockade Using Nintedanib for Esophagogastric Cancer. Won, E., Basunia, A., Chatila, WK., et al.[2020]

In a study of 20 esophageal squamous cell carcinomas (ESCC), DNA microarrays identified amplification of eight oncogenes in 9 tumors, highlighting the potential for targeted therapies based on these genetic alterations.

The research demonstrated that while DNA microarrays can detect specific oncogene amplifications, not all amplified genes corresponded to DNA copy number gains identified by conventional comparative genomic hybridization (CGH), suggesting that microarrays provide a more detailed analysis of oncogene amplification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of amplified oncogenes by genome DNA microarrays in human primary esophageal squamous cell carcinoma: comparison with conventional comparative genomic hybridization analysis. Arai, H., Ueno, T., Tangoku, A., et al.[2019]

In a study of 31 esophageal cancer specimens, epidermal growth factor receptor (EGFr) was found in both cancer and normal tissues, with a trend suggesting higher levels in cancer, but no significant differences were noted between the two.

The erbB2 protein (p185) was consistently detected in all samples, showing higher expression in adenocarcinomas compared to squamous cell carcinomas, indicating its potential relevance specifically in adenocarcinoma cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidermal growth-factor receptors and erbb2 protein expression in esophageal cancer and normal mucosa. Dittadi, R., Ruol, A., Gion, M., et al.[2019]

In a study of 60 patients with EGFR-amplified gastroesophageal adenocarcinoma (GEA), treatment with epidermal growth factor receptor inhibitors (EGFRi) resulted in a 43% objective response rate and a median progression-free survival of 4.6 months.

Patients receiving EGFRi showed significantly improved overall survival compared to those on non-EGFRi therapies, with median overall survival times of 20.6 months for first-line therapy, indicating a strong therapeutic benefit, although only 5% of eligible patients received EGFRi.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidermal Growth Factor Receptor Inhibition in Epidermal Growth Factor Receptor-Amplified Gastroesophageal Cancer: Retrospective Global Experience. Maron, SB., Moya, S., Morano, F., et al.[2023]

A rare case of co-amplification of both EGFR and ERBB2 was identified in a 72-year-old man with esophageal squamous cell carcinoma, which is typically characterized by mutually exclusive amplification of these genes.

The tumor exhibited three distinct cancer-cell populations, each with different amplification patterns, suggesting a complex progression of genetic instability leading to the unique co-amplification observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overexpression and gene amplification of both ERBB2 and EGFR in an esophageal squamous cell carcinoma revealed by fluorescence in situ hybridization, multiplex ligation-dependent probe amplification and immunohistochemistry. Oyama, T., Okamoto, K., Nakamura, R., et al.[2019]

References

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

PD-1 inhibitors versus chemotherapy as second-line treatment for advanced esophageal squamous cell carcinoma: a meta-analysis. [2022]

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

Nivolumab Plus Erlotinib in Patients With EGFR-Mutant Advanced NSCLC. [2019]

3. Ireland pubmed.ncbi.nlm.nih.gov

Bevacizumab and erlotinib (BE) first-line therapy in advanced non-squamous non-small-cell lung cancer (NSCLC) (stage IIIB/IV) followed by platinum-based chemotherapy (CT) at disease progression: a multicenter phase II trial (SAKK 19/05). [2018]

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

FGFR2-Altered Gastroesophageal Adenocarcinomas Are an Uncommon Clinicopathologic Entity with a Distinct Genomic Landscape. [2020]

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

Efficacy of Combined VEGFR1-3, PDGFα/β, and FGFR1-3 Blockade Using Nintedanib for Esophagogastric Cancer. [2020]

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

Detection of amplified oncogenes by genome DNA microarrays in human primary esophageal squamous cell carcinoma: comparison with conventional comparative genomic hybridization analysis. [2019]

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

Epidermal growth-factor receptors and erbb2 protein expression in esophageal cancer and normal mucosa. [2019]

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

Epidermal Growth Factor Receptor Inhibition in Epidermal Growth Factor Receptor-Amplified Gastroesophageal Cancer: Retrospective Global Experience. [2023]

9. Australia pubmed.ncbi.nlm.nih.gov

Overexpression and gene amplification of both ERBB2 and EGFR in an esophageal squamous cell carcinoma revealed by fluorescence in situ hybridization, multiplex ligation-dependent probe amplification and immunohistochemistry. [2019]