MK-1200 for Solid Tumors

Recruiting at 15 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: Corticosteroids, Anticancer agents

Disqualifiers: Severe digestive disease, Uncontrolled diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 15 months

304 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the efficacy and safety of MK-1200 monotherapy in participants with advanced/metastatic gastric/gastroesophageal junction (GEJ) cancer, esophageal cancer, biliary tract cancer, and pancreatic ductal adenocarcinoma who have received, or been intolerant to, all treatments known to confer clinical benefit. Part 1 of the study will be a dose escalation to determine the maximum tolerated dose (MTD). Part 2 will evaluate safety and efficacy of MK-1200 at 2 different doses

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received prior systemic anticancer therapy within 4 weeks before the study, which might imply a need to stop certain treatments. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of the drug MK-1200 for solid tumors?

Research on similar treatments suggests that targeting MK2, a component related to MK-1200, has shown promise in treating multiple myeloma by inhibiting tumor growth and improving survival in mouse models. Additionally, higher MK2 levels have been linked to better chemotherapy responses and survival in lung cancer patients, indicating potential benefits for solid tumors. ^{1 2 3 4 5}

What safety data exists for MK-1200 or similar treatments in humans?

There is no specific safety data available for MK-1200, but similar treatments like MK-2206 have been studied. In a study of MK-2206, common side effects included mild diarrhea, skin rash, nausea, fatigue, and high blood sugar, suggesting it is generally safe with mostly mild side effects. ^{6 7 8 9 10}

How is the drug MK-1200 different from other treatments for solid tumors?

The drug MK-1200 is unique because it may involve components like CKD-602, a camptothecin derivative known for its ability to inhibit tumor growth by inducing cell death in cancer cells, and CKD-516, a vascular disrupting agent that targets the blood vessels supplying the tumor, potentially offering a novel approach compared to standard treatments. ^{2 11 12 13 14}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with advanced solid tumors like stomach, esophagus, biliary tract, or pancreatic cancers who've tried all other treatments without success. They should be recovered from previous treatment side effects and have controlled HIV or hepatitis if present.

Inclusion Criteria

I have recovered from side effects of previous cancer treatments.

My cancer is advanced and cannot be removed by surgery.

My HIV is well controlled with medication.

Exclusion Criteria

I have a severe digestive condition.

I have a history of serious heart diseases.

Cardiac pacemaker use

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of MK-1200 via IV infusion every 2 weeks to determine the maximum tolerated dose (MTD)

Up to 28 days

Bi-weekly visits (in-person)

Treatment

Participants receive MK-1200 at determined doses via IV infusion every 2 weeks

Up to 15 months

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• MK-1200

Trial Overview MK-1200 is being tested to see how safe and effective it is for certain advanced cancers. The study has two parts: first finding the highest dose patients can take without serious side effects (MTD), then testing this dose's safety and effectiveness.

Participant Groups

Group I: Part 2: MK-1200 Cohort B Experimental Treatment 2 Interventions

In Part 2, participants in Cohort B will receive Dose 1 of MK-1200 via IV infusion Q2W until any discontinuation criteria are met.

Group II: Part 2: MK-1200 Cohort A Experimental Treatment 2 Interventions

In Part 2, participants in Cohort A will receive either Dose 1 or Dose 2 of MK-1200 via IV infusion Q2W until any discontinuation criteria are met.

Group III: Part 1: MK-1200 Experimental Treatment 2 Interventions

In Part 1, participants will receive escalating doses of MK-1200 via intravenous (IV) infusion every 2 weeks (Q2W) until any discontinuation criteria are met.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

MK-0888, a VEGFR-2 inhibitor, was generally well tolerated in both healthy volunteers and cancer patients at doses up to 100 mg, indicating a favorable early safety profile.

However, the pharmacokinetic analysis revealed that MK-0888 did not achieve the necessary drug levels for efficacy, suggesting that further development of this compound may not be warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/pharmacodynamic-based decision making in the development of MK-0888, a VEGFR-2/FLT-3 kinase inhibitor. Iwamoto, M., Friedman, EJ., Sepp-Lorenzino, L., et al.[2015]

In a study involving 20 Japanese patients with advanced colorectal cancer, the combination of MK-0646 with cetuximab and irinotecan was found to be well tolerated, with only one patient experiencing a dose-limiting toxicity (grade 3 hyperglycemia).

The combination therapy increased the exposure of MK-0646 by 25% without affecting the pharmacokinetics of cetuximab and irinotecan, although it did reduce the levels of SN-38, the active metabolite of irinotecan, indicating minimal drug interactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 pharmacokinetic study of MK-0646 (dalotuzumab), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in combination with cetuximab and irinotecan in Japanese patients with advanced colorectal cancer. Doi, T., Muro, K., Yoshino, T., et al.[2021]

In a phase II study involving 14 patients with advanced uterine serous carcinoma (USC), the AKT inhibitor MK-2206 showed limited efficacy, with a clinical benefit rate of 14.3% and a median progression-free survival of only 2 months.

Despite the overall limited activity, one patient achieved a partial response and remained progression-free for 6 months, suggesting that some patients may benefit from this treatment, warranting further research to identify responsive patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of MK-2206, an AKT inhibitor, in uterine serous carcinoma. Stover, EH., Xiong, N., Myers, AP., et al.[2022]

The maximum-tolerated dose (MTD) of MK-0457, a novel pan-Aurora kinase inhibitor, was determined to be 64 mg/m²/h, with dose-limiting toxicities including severe neutropenia and herpes zoster observed at higher doses.

MK-0457 was generally well tolerated, with nearly half of the 27 patients experiencing stable disease, suggesting potential efficacy, particularly in combination with other cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors. Traynor, AM., Hewitt, M., Liu, G., et al.[2022]

The maximum-tolerated dose (MTD) of CKD-516, a new vascular disrupting agent, was established at 12 mg/m²/day, with safety evaluations revealing manageable side effects primarily related to gastrointestinal issues and hypertension.

In a study of 23 patients with advanced solid tumors, CKD-516 demonstrated preliminary antitumor efficacy, with 26.1% of patients achieving stable disease and a median progression-free survival of 39 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of CKD-516, a Novel Vascular Disrupting Agent, in Patients with Advanced Solid Tumors. Oh, DY., Kim, TM., Han, SW., et al.[2018]

References

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

Midkine translocated to nucleoli and involved in carcinogenesis. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetic/pharmacodynamic-based decision making in the development of MK-0888, a VEGFR-2/FLT-3 kinase inhibitor. [2015]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting MK2 Is a Novel Approach to Interfere in Multiple Myeloma. [2020]

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

Tumor MK2 transcript levels are associated with improved response to chemotherapy and patient survival in non-small cell lung cancer. [2023]

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

Midkine neurite growth-promoting factor 2 expression as a potential prognostic marker of adjuvant therapy in head and neck squamous cell carcinoma. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Phase 1 pharmacokinetic study of MK-0646 (dalotuzumab), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in combination with cetuximab and irinotecan in Japanese patients with advanced colorectal cancer. [2021]

7. Iran pubmed.ncbi.nlm.nih.gov

Evaluating the Effects of Separate and Concomitant Use of MK-2206 and Salinomycin on Prostate Cancer Cell Line. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

A phase II study of MK-2206, an AKT inhibitor, in uterine serous carcinoma. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors. [2022]

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

A phase I trial of MK-2206 in children with refractory malignancies: a Children's Oncology Group study. [2021]

11. Scotland pubmed.ncbi.nlm.nih.gov

Antitumor activity of CKD-602, a camptothecin derivative, in a mouse glioma model. [2013]

12. Korea (South) pubmed.ncbi.nlm.nih.gov

Phase I Study of CKD-516, a Novel Vascular Disrupting Agent, in Patients with Advanced Solid Tumors. [2018]

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

A dose escalation, safety, and tolerability study of MN-029 in patients with advanced solid tumors. [2021]

14. Greece pubmed.ncbi.nlm.nih.gov

CKD-602, a camptothecin derivative, inhibits proliferation and induces apoptosis in glioma cell lines. [2013]