Individualized Cancer Therapy for Aggressive Cancers

(MCW I-PREDICT Trial)

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Medical College of Wisconsin

Disqualifiers: Uncontrolled diabetes, Chronic renal disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 months

400 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a prospective, open-label navigational investigation designed to evaluate the feasibility of using molecular profile-based evidence to determine individualized cancer therapy for patients with aggressive malignancies. This is a non-randomized, histology-agnostic trial. Although there will be a case mix of histologies, the investigators now know that individual histologies are composed of a heterogeneous mix of molecular alterations. It is not clear whether one case mix is better or worse than another. Thus, the investigators are testing a strategy of molecular matching that may apply across different cancers.

Will I have to stop taking my current medications?

The trial requires that you stop taking other anti-tumor agents for at least five half-lives of the agent or two weeks, whichever is shorter, before enrolling in Group 3. You must not have been treated with anti-tumor agents to enroll in Group 1 or Group 2. Additionally, you must be off prior antibody therapy for at least three half-lives before starting treatment.

What data supports the effectiveness of the drug Keytruda (pembrolizumab) for treating aggressive cancers?

Keytruda (pembrolizumab) has shown effectiveness in treating various cancers, including non-small cell lung cancer and melanoma, by helping the immune system attack cancer cells. It is approved for use in advanced melanoma and certain types of lung cancer, indicating its potential benefit in aggressive cancers. ^{1 2 3 4 5}

How is the drug pembrolizumab (Keytruda) unique in treating aggressive cancers?

Pembrolizumab (Keytruda) is unique because it is an immunotherapy drug that targets the PD-1 receptor, helping the immune system recognize and attack cancer cells. This mechanism is different from traditional chemotherapy, which directly kills cancer cells, and it has shown effectiveness in various cancers, including those with high PD-L1 expression. ^{2 3 4 5 6}

Research Team

Ben George, MD

Principal Investigator

Medical College of Wisconsin

Razelle Kurzrock, MD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

Adults with aggressive solid tumors, including rare cancers or those without beneficial standard therapies. Eligible participants must have measurable disease, adequate organ function, and not be pregnant or breastfeeding. They should agree to use contraception and have no severe medical conditions that could interfere with the study.

Inclusion Criteria

I am 18 years old or older.

Patient is either: Treatment naïve for their newly diagnosed malignancy, or Status post one or more systemic therapy regimens. Patient must have measurable disease for malignancy. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. New York Heart Association (NYHA) Functional Classification I-II. Adequate organ and marrow function as defined. Able to swallow and retain oral medication. If actionable or appropriate molecular profiling has not already been performed, patient must have or provide evaluable tissue and/or blood for molecular profiling. Pregnancy: Female subjects should avoid becoming pregnant, and male subjects should avoid impregnating a female partner. Ability to understand a written informed consent document, and the willingness to sign it. Patients presented at Molecular Tumor Board (MTB) up to two weeks prior to signing consent are eligible to be treated on study based on the MTB recommendations.

I have a serious cancer with limited treatment options or a rare type with no approved treatments.

Exclusion Criteria

I do not have any severe illnesses that could affect the study's results.

I have not had brain radiation within the last 14 days.

Two oncologists disagree on prognosis or resectability

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Molecular Profiling

Tumor tissues/blood are molecularly profiled to determine individualized cancer therapy

4 weeks

Treatment

Participants receive either matched therapy recommended by the Molecular Tumor Board or unmatched therapy based on the treating physician's choice

8 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Standard of care agent
• Targeted agent

Trial Overview The trial is testing personalized cancer treatments based on molecular profiling of individual tumors against standard care agents. It's a non-randomized study aiming to see if matching therapy to specific molecular changes in different cancers can improve outcomes.

Participant Groups

Group I: Group 3: Targeted agent Experimental Treatment 1 Intervention

Subjects will be grouped into one of three study groups (Groups 1, 2, or 3) based on their disease status and history of prior cancer therapy. Group 3 will comprise subjects with metastatic or unresectable disease who have received at least one prior systemic therapy, whether matched or unmatched.

Group II: Group 3: Standard of care agent Experimental Treatment 1 Intervention

Subjects will be grouped into one of three study groups (Groups 1, 2, or 3) based on their disease status and history of prior cancer therapy. Group 3 will comprise subjects with metastatic or unresectable disease who have received at least one prior systemic therapy, whether matched or unmatched.

Group III: Group 2: Targeted agent Experimental Treatment 1 Intervention

Subjects will be grouped into one of three study groups (Groups 1, 2, or 3) based on their disease status and history of prior cancer therapy. Group 2 will comprise treatment naïve subjects with metastatic disease.

Group IV: Group 2: Standard of care agent Experimental Treatment 1 Intervention

Subjects will be grouped into one of three study groups (Groups 1, 2, or 3) based on their disease status and history of prior cancer therapy. Group 2 will comprise treatment naïve subjects with metastatic disease.

Group V: Group 1: Targeted agent Experimental Treatment 1 Intervention

Subjects will be grouped into one of three study groups (Groups 1, 2, or 3) based on their disease status and history of prior cancer therapy. Group 1 subjects will comprise treatment naïve subjects with localized disease and (i) are eligible for neoadjuvant treatment, (ii) have unresectable disease, or (iii) are medically unfit for surgical resection.

Group VI: Group 1: Standard of care agent Experimental Treatment 1 Intervention

Subjects will be grouped into one of three study groups (Groups 1, 2, or 3) based on their disease status and history of prior cancer therapy. Group 1 subjects will comprise treatment naïve subjects with localized disease and (i) are eligible for neoadjuvant treatment, (ii) have unresectable disease, or (iii) are medically unfit for surgical resection.

Standard of care agent is already approved in United States, European Union for the following indications:

Approved in United States as Keytruda for:

• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Microsatellite instability-high (MSI-H) cancer
• Gastric or gastroesophageal junction adenocarcinoma
• Esophageal or gastroesophageal junction carcinoma
• Cervical cancer
• Hepatocellular carcinoma (HCC)
• Merkel cell carcinoma (MCC)
• Small cell lung cancer (SCLC)

Approved in European Union as Keytruda for:

• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Microsatellite instability-high (MSI-H) cancer
• Gastric or gastroesophageal junction adenocarcinoma
• Esophageal or gastroesophageal junction carcinoma
• Cervical cancer
• Hepatocellular carcinoma (HCC)
• Merkel cell carcinoma (MCC)
• Small cell lung cancer (SCLC)

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Findings from Research

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

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

Pembrolizumab: first global approval. [2021]

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

New Approved Use for Keytruda. [2022]

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

6. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]