STK-012 + Pembrolizumab for Cancer

(SYNERGY-101 Trial)

Recruiting at 30 trial locations

Overseen By Synthekine STK-012-101 Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

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

364 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, STK-012, both alone and with other cancer drugs like pembrolizumab (KEYTRUDA), to determine its safety and effectiveness for advanced solid tumors. The trial includes different parts: some use STK-012 alone, while others combine it with pembrolizumab and other chemotherapy drugs. It targets individuals whose cancer has worsened after standard treatments or who cannot tolerate or choose to avoid those treatments. Those with specific types of tumors, particularly if untreated for metastatic disease, might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering the opportunity to be among the first to receive this new drug.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that STK-012 has been tested on 47 patients as a standalone treatment. These early studies aimed to find the highest safe dose. So far, results suggest that STK-012 is generally well-tolerated.

When combined with pembrolizumab, STK-012 is still under evaluation to ensure safety. The goal is to find a dose that works effectively without causing serious side effects. Researchers aim to balance treatment effectiveness with safety.

STK-012 is also being studied with pembrolizumab, pemetrexed, and carboplatin. These drugs have been used together before, especially for certain lung cancers, and have shown an acceptable safety level.

In this early research phase, the main focus is on how well patients handle these treatments. Since this is the first phase of human studies, safety findings are still being collected and reviewed. Ongoing research aims to find a treatment plan that reduces risks while increasing potential benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most cancer treatments involve chemotherapy or immunotherapy that work by either killing rapidly dividing cells or boosting the immune system to attack cancer cells. The treatments being explored, STK-012 and pembrolizumab, are unique because STK-012 is a novel agent thought to enhance the immune response against cancer. Researchers are excited about STK-012 because it can be administered subcutaneously, potentially offering a more convenient delivery method than traditional intravenous therapies. Additionally, the combination with pembrolizumab, an established immunotherapy, could amplify the immune system's ability to target and destroy cancer cells, offering new hope for patients with advanced cancers.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that the drug STK-012, one of the treatments in this trial, has potential in treating advanced solid tumors when used alone. Early results suggest it increases certain proteins that aid the immune system and promotes the growth of specific T cells, which play a crucial role in fighting cancer. In this trial, some participants will receive STK-012 combined with pembrolizumab, a current cancer medication. Researchers believe these treatments might work better together than separately. Pembrolizumab has already demonstrated benefits in effectiveness and duration in previous studies. Additionally, this trial is examining the combination of STK-012, pembrolizumab, pemetrexed, and carboplatin for its potential effectiveness in certain types of cancer, particularly in patients whose tumors are PD-L1 negative, indicating they might respond well to this treatment. ^{2 4 6 7 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: Phase 2: Arm B Experimental Treatment 4 Interventions

STK-012 1.5 mg SC Q3W + SoC IV in first-line PD-L1 negative NSQ NSCLC

Group II: Phase 2: Arm A Experimental Treatment 4 Interventions

STK-012 2.25 mg SC Q3W + SoC IV in first-line PD-L1 negative NSQ NSCLC

Group III: Phase 1b: STK-012 monotherapy expansion Experimental Treatment 1 Intervention

STK-012 SC monotherapy in selected solid tumor indications

Group IV: Phase 1b: STK-012 + pembrolizumab dose expansion Experimental Treatment 2 Interventions

STK-012 SC will be administered in combination with pembrolizumab IV in selected solid tumor indications

Group V: Phase 1b: STK-012 + SoC dose expansion Experimental Treatment 4 Interventions

STK-012 SC + SoC IV in first-line PD-L1 negative NSQ NSCLC

Group VI: Phase 1a: STK-012 monotherapy dose escalation Experimental Treatment 1 Intervention

STK-012 subcutaneous (SC) as monotherapy in selected solid tumor indications

Group VII: Phase 1a: STK-012 + standard of care (SoC) dose escalation Experimental Treatment 4 Interventions

STK-012 SC + SoC IV in first-line non-squamous (NSQ) NSCLC

Group VIII: Phase 1a: STK-012 + pembrolizumab dose escalation Experimental Treatment 2 Interventions

STK-012 SC + pembrolizumab intravenously (IV) in selected solid tumor indications

Group IX: Phase 2: Arm C Active Control 3 Interventions

SoC IV in first-line PD-L1 negative NSQ NSCLC

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

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]

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) 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 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, 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, 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]

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 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]

Citations

1. firstwordpharma.com firstwordpharma.com/story/6511095

Synthekine Announces Late-Breaking Oral Presentation of ... In this study, STK-012 is being evaluated in combination with standard-of-care pembrolizumab + chemotherapy in first-line, PD-L1 negative ...

2. aacrjournals.org aacrjournals.org/cancerres/article/82/12_Supplement/CT244/702741/Abstract-CT244-A-phase-1a-1b-study-of-STK-012-an

Abstract CT244: A phase 1a/1b study of STK-012, an α/β IL-2 ... STK-012 is in development as monotherapy and in combination with pembrolizumab for the treatment of advanced solid tumors.

3. merck.com merck.com/news/updated-findings-from-keynote-012-for-keytruda-pembrolizumab-show-continued-benefit-in-response-rates-and-duration-of-response-lasting-up-to-30-months-in-patients-with-previously-treated-recur/

Updated Findings from KEYNOTE-012 for KEYTRUDA® ... The secondary endpoint results showed a median overall survival (OS) rate of eight months (95% CI, 6-10) (Abstract #6012). The phase 1b KEYNOTE-012 study was ...

4. mskcc.org mskcc.org/cancer-care/clinical-trials/22-166

A Phase I Study of STK-012 Alone and ... Researchers believe both drugs used together may be more effective against advanced solid tumors than either one alone. STK-012 is given as a subcutaneous ( ...

5. cancer.columbia.edu cancer.columbia.edu/cancer-types-care/clinical-trials/find-clinical-trial/phase-1-2-study-evaluate-stk-012-single-agent-and-combination-therapy-subjects-front-line-advanced-nsclc-and-other-selected-indications

A Phase 1/2 Study to Evaluate STK 012 as a Single Agent and ... The main purpose of this study is to determine the highest dose of STK-012 that can be given safely alone and in combination with a standard dose of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05098132?term=AREA%5BNCTIdSearch%5D(NCT05098132)&rank=1

STK-012 Monotherapy and in Combination Therapy ... Participants enrolled to STK-012 + pembrolizumab combination dose expansion must have selected tumor types and may not have received treatment for metastatic ...

7. merck.com merck.com/news/merck-and-eisai-provide-update-on-phase-3-leap-012-trial-in-unresectable-non-metastatic-hepatocellular-carcinoma/

Merck and Eisai Provide Update on Phase 3 LEAP-012 ... As reported previously, KEYTRUDA plus LENVIMA in combination with TACE met the study's other primary endpoint of progression-free survival ...

8. yalemedicine.org yalemedicine.org/clinical-trials/stk-012-101-phase-1a-1b-study-of-stk-012-monotherapy-and-in-combination-with-pembrolizumab-in-patie

A Phase 1a/1b Study to Evaluate the Safety and ... This is a first-in-human, phase 1a/1b, multicenter, open-label, dose escalation study of STK-012 as monotherapy and in combination with pembrolizumab.