TROP2 ADC for Cancer

(MK-2870-001 Trial)

Recruiting at 154 trial locations

Overseen By Study Manager

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Klus Pharma Inc.

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Cardiac disease, Brain metastases, Liver disease, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

1410 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

A Phase I-II, First-in-Human Study of SKB264 (Sac-TMT; MK-2870) in Patients with Locally Advanced Unresectable/Metastatic Solid Tumors who are refractory to Available Standard Therapies. Patient must have historically documented, incurable, locally advanced or metastatic cancer that are refractory to standard therapies of one of the following types: 1. Triple negative breast cancer 2. Epithelial ovarian cancer 3. Non-small cell lung cancer 4. Gastric adenocarcinoma/Gastroesophageal junction adenocarcinoma 5. Small cell lung cancer 6. HR+/ HER2-breast cancer 7. Head and neck squamous cell carcinoma 8. Endometrial carcinoma 9. Urothelial carcinoma 10. Cervical cancer

Will I have to stop taking my current medications?

The trial requires that you stop any standard cancer therapy or experimental therapy at least 4 weeks or five half-lives before starting the study drug. Additionally, you cannot use strong inhibitors or inducers of CYP3A4 at least 14 days prior to and throughout the study.

What makes the drug SKB264 (MK-2870) unique for cancer treatment?

SKB264 (MK-2870) is unique because it targets Trop-2, a protein overexpressed in many cancers, using an antibody-drug conjugate (ADC) approach. This allows it to deliver chemotherapy directly to cancer cells, potentially reducing side effects and improving effectiveness compared to traditional chemotherapy. ^{1 2 3 4 5}

Who Is on the Research Team?

Jordi Rodon Ahnert, MD, PhD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults aged 18-75 with advanced solid tumors that can't be surgically removed or have spread and don't respond to standard treatments. Specific cancers include certain types of breast, ovarian, lung, gastric, head and neck, endometrial, and urothelial cancers. Participants must have acceptable organ function and blood counts, not require oxygen for daily activities or have severe heart conditions.

Inclusion Criteria

Patients must be able to provide documented voluntary informed consent

Your white blood cell count, platelet count, and hemoglobin levels are within a certain range.

I am fully active or can carry out light work.

Exclusion Criteria

I haven't taken any experimental drugs within the last 4 weeks.

The investigator considers other situations that patients are not appropriate to participate in this trial

I have been treated with TROP 2 targeted therapies before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I: Dose Escalation

Participants receive SKB264 as a single IV infusion at escalating dose levels to determine the maximum tolerated dose (MTD) and recommended doses for expansion (RDEs).

12 months

Every 2 weeks in 4-week cycles

Phase II: Treatment

Participants receive SKB264 at the recommended dose levels for expansion to evaluate the objective response rate (ORR) and other efficacy measures.

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and overall survival.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• SKB264

Trial Overview SKB264 is being tested in this Phase I-II trial on patients with various advanced solid tumors unresponsive to standard therapies. The study aims to evaluate the safety and effectiveness of SKB264 as a potential treatment option for these patients.

How Is the Trial Designed?

Group I: Phase II: Urothelial carcinoma Experimental Treatment 1 Intervention

Histologically or cytologically documented, incurable, locally advanced or metastatic cancer

Group II: Phase II: Triple Negative Breast Cancer Experimental Treatment 1 Intervention

Histologically documented or cytologically , incurable, locally advanced or metastatic cancer

Group III: Phase II: Non-Small Cell Lung Cancer Experimental Treatment 1 Intervention

Histologically documented or cytologically, incurable, locally advanced or metastatic cancer

Group IV: Phase II: Head and Neck Squamous Cell Carcinoma Experimental Treatment 1 Intervention

Histologically documented or cytologically, incurable, locally advanced or metastatic cancer

Group V: Phase II: HR+/ HER2- Breast Cancer Experimental Treatment 1 Intervention

Histologically documented or cytologically, incurable, locally advanced or metastatic cancer

Group VI: Phase II: Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma Experimental Treatment 1 Intervention

Histologically or cytologically documented, incurable, locally advanced or metastatic cancer

Group VII: Phase II: Extensive-stage Small Cell Lung Cancer Experimental Treatment 1 Intervention

Histologically documented or cytologically, incurable, locally advanced or metastatic cancer

Group VIII: Phase II: Epithelial Ovarian Cancer Experimental Treatment 1 Intervention

Histologically documented or cytologically, incurable, locally advanced or metastatic cancer

Group IX: Phase II: Endometrial carcinoma Experimental Treatment 1 Intervention

Histologically documented or cytologically, incurable, locally advanced or metastatic cancer

Group X: Phase II: Cervical Cancer Experimental Treatment 1 Intervention

Histologically or cytologically documented, incurable, locally advanced or metastatic cancer

Group XI: Phase I: Dose Escalation Experimental Treatment 1 Intervention

Five dose levels have been selected for evaluation in the Phase I part of the study: 2, 4, 6, 9, and 12 mg/kg of SKB264

SKB264 is already approved in China, European Union, United States for the following indications:

Approved in China as SKB264 for:

• Triple-negative breast cancer
• EGFR-mutated non-small cell lung cancer

Approved in European Union as SKB264 for:

• Clinical trials approved but no specific indications listed yet

Approved in United States as SKB264 for:

• Clinical trials ongoing but no specific indications approved yet

Who Is Running the Clinical Trial?

Klus Pharma Inc.

Lead Sponsor

Trials

4

Recruited

2,100+

Published Research Related to This Trial

Trop-2 is a promising target for cancer treatment because it is overexpressed in many tumor types, making it suitable for targeted therapies like antibody-drug conjugates (ADCs).

Early-phase clinical trials have shown that Trop-2-targeted ADCs are safe and effective, particularly in hard-to-treat cancers such as triple-negative breast cancer and small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Trop-2 in solid tumors: future prospects. Zaman, S., Jadid, H., Denson, AC., et al.[2023]

Trophoblast surface antigen 2 (Trop-2) is a promising target for cancer therapy due to its high expression in various tumors compared to normal tissues, playing a key role in tumor growth and progression.

Antibody-drug conjugates (ADCs) targeting Trop-2, such as Sacituzumab Govitecan and Datopotamab Deruxtecan, have shown strong antitumor activity and potential for enhancing the effectiveness of other cancer treatments by reprogramming the tumor microenvironment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Trop-2 in cancer: Recent research progress and clinical application. Qiu, S., Zhang, J., Wang, Z., et al.[2023]

Trop2 is a glycoprotein that is overexpressed in many cancers, playing a role in cell self-renewal and survival, and its overexpression is linked to drug resistance, making it a significant prognostic biomarker.

Therapeutic strategies targeting Trop2, including antibodies and nanoparticles, have shown promising results in pre-clinical studies by significantly inhibiting tumor growth, with ongoing clinical trials exploring its efficacy in treating epithelial cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. Shvartsur, A., Bonavida, B.[2022]

Trop-2 is highly expressed in pancreatic cancer tissues compared to peritumoral tissues, with an expression rate of 87.1% in tumors versus 9.7% in surrounding tissues, indicating its potential role in cancer development.

The high expression of Trop-2 is associated with lower differentiation in pancreatic cancer, suggesting it could serve as a clinical prognostic marker and a potential therapeutic target for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Expression and clinical significance of Trop-2 in human pancreatic cancer]. Qiu, JR., Tang, Q., Lin, H., et al.[2011]

Trop2 is a protein that is overexpressed in many cancers, making it a promising target for cancer therapies, particularly in metastatic triple-negative breast cancer where the anti-Trop2 drug Trodelvy™ has been approved.

Research is ongoing to explore the effectiveness of Trop2-targeted treatments in other types of tumors, as the expression and role of Trop2 can vary significantly across different cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Trop2-targeted therapy: Novel agents and opportunities beyond breast cancer. Liu, X., Deng, J., Yuan, Y., et al.[2023]

Citations

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

Targeting Trop-2 in solid tumors: future prospects. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Targeting Trop-2 in cancer: Recent research progress and clinical application. [2023]

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

Trop2 and its overexpression in cancers: regulation and clinical/therapeutic implications. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Expression and clinical significance of Trop-2 in human pancreatic cancer]. [2011]

5. England pubmed.ncbi.nlm.nih.gov

Advances in Trop2-targeted therapy: Novel agents and opportunities beyond breast cancer. [2023]