STK-012 + Pembrolizumab for Cancer

Recruiting at 19 trial locations

Overseen By Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Synthekine

Must not be taking: Small molecule inhibitors

Disqualifiers: Recent radiotherapy, IL-2/IL-15 therapy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

202 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new drug called STK-012 alone and with another medication in patients with advanced solid tumors that haven't responded to usual treatments. The aim is to find the right dose and see how well it works.

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anti-cancer therapy at least 3 weeks before starting the study treatment. If you are taking small molecule kinase inhibitors, you must stop them within 6 elimination half-lives before the first dose. Other medications are not specified, so it's best to discuss with the trial team.

Is the combination of STK-012 and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, has been used in cancer treatment and is generally considered safe, but it can cause side effects like fatigue, nausea, and immune-related issues such as thyroid problems and, rarely, type 1 diabetes. While specific safety data for the combination with STK-012 is not provided, pembrolizumab's safety profile is well-documented in various cancers. ^{1 2 3 4 5}

What makes the drug STK-012 + Pembrolizumab unique for cancer treatment?

The combination of STK-012 and Pembrolizumab is unique because it involves using Pembrolizumab, a PD-1 inhibitor that helps the immune system attack cancer cells, in combination with STK-012, which may enhance this effect. This approach is different from standard treatments as it targets the immune system's interaction with cancer, potentially offering a new way to treat cancers that express PD-L1. ^{1 4 6 7 8}

What data supports the effectiveness of the drug pembrolizumab in treating cancer?

Pembrolizumab has been shown to improve survival rates in patients with non-small cell lung cancer and melanoma by helping the immune system attack cancer cells more effectively. It has been approved by the FDA for certain types of lung cancer and melanoma, demonstrating significant improvements in patient outcomes compared to traditional chemotherapy. ^{1 2 4 6 8}

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced solid tumors who have tried standard treatments without success, can't tolerate them, or chose not to use them. They must provide a tumor tissue sample and if they have brain metastases, these should be treated and stable. People can't join if they've had recent cancer therapy or radiotherapy.

Inclusion Criteria

My cancer has worsened after standard treatment, or I couldn't tolerate or chose not to undergo standard treatment.

I can provide a sample of my tumor, or I agree to a new biopsy if needed.

I have had treatment for brain metastases and do not have symptoms.

Exclusion Criteria

I have received IL-2 or IL-15 therapy before.

I have recently had radiotherapy for cancer outside of the brain.

I haven't taken any cancer drugs or small molecule inhibitors recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

STK-012 is administered in sequential ascending doses as monotherapy and in combination therapy to determine the maximum tolerated dose and/or the recommended phase 2 dose

21 days per cycle

Dose Expansion

STK-012 is administered at the recommended phase 2 dose as monotherapy and in combination therapy to evaluate safety and efficacy

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• STK-012

Trial Overview The study tests STK-012 alone and combined with Pembrolizumab in patients with specific solid tumors. It's the first time humans are trying STK-012, starting with low doses that increase gradually to find the safest dose that works best when given together.

How Is the Trial Designed?

Group I: Part F: STK-012 Q3W + pembrolizumab, pemetrexed and carboplatin dose expansion Experimental Treatment 4 Interventions

STK-012 will be administered at the RP2D SC in combination with pembrolizumab IV Q3W, pemetrexed IV Q3W and carboplatin IV Q3W until unacceptable toxicity, disease progression, or withdrawal of consent.

Group II: Part E: STK-012 Q3W + pembrolizumab, pemetrexed and carboplatin dose escalation Experimental Treatment 4 Interventions

STK-012 will be administered in sequential ascending doses SC Q3W in combination with pembrolizumab IV Q3W, pemetrexed IV Q3W and carboplatin IV Q3W until unacceptable toxicity, disease progression, or withdrawal of consent.

Group III: Part D: STK-012 Q3W monotherapy and STK-012 Q3W + pembrolizumab dose expansions Experimental Treatment 2 Interventions

STK-012 will be administered at the RP2D SC as monotherapy and in combination with a fixed dose of pembrolizumab IV Q3W until unacceptable toxicity, disease progression, or withdrawal of consent.

Group IV: Part C: STK-012 Q3W + pembrolizumab dose escalation Experimental Treatment 2 Interventions

STK-012 will be administered in sequential ascending doses SC Q3W in combination with a fixed dose of pembrolizumab intravenously (IV) Q3W until unacceptable toxicity, disease progression, or withdrawal of consent.

Group V: Part B: STK-012 every three weeks (Q3W) monotherapy dose escalation Experimental Treatment 1 Intervention

STK-012 will be administered in sequential ascending doses as monotherapy SC Q3W until unacceptable toxicity, disease progression, or withdrawal of consent.

Group VI: Part A: STK-012 weekly (QW) monotherapy dose escalation Experimental Treatment 1 Intervention

STK-012 will be administered in sequential ascending doses as monotherapy subcutaneously (SC) QW until unacceptable toxicity, disease progression, or withdrawal of consent.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Synthekine

Lead Sponsor

Trials

3

Recruited

290+

Published Research Related to This Trial

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 (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]

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 is a monoclonal antibody that effectively blocks the PD-1 receptor on T cells, enhancing their ability to attack cancer cells, particularly in melanoma patients.

In a Phase I study involving 411 patients, pembrolizumab demonstrated high durable response rates with minimal toxicity, indicating its potential as a safe and effective treatment option for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. Hersey, P., Gowrishankar, K.[2017]

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 advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

Citations

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. 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]

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

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

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

Pembrolizumab joins the anti-PD-1 armamentarium in the treatment of melanoma. [2017]

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

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

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]