CDK7 Inhibitor for Cancer

Recruiting at 14 trial locations

Overseen By Qurient Clinical Trial Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Qurient Co., Ltd.

Disqualifiers: Cardiac disease, Infections, Autoimmune, 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

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment called Q901 (a CDK7 inhibitor), both alone and with pembrolizumab. Researchers aim to assess the safety of these treatments and their effectiveness against various advanced or metastatic cancers, such as ovarian or colorectal cancer, that have not responded to standard treatments. Suitable candidates for this trial include individuals with specific cancer types that have progressed despite other therapies. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that Q901, a drug under study, underwent testing in early trials. These trials involved a small number of patients, and some experienced stable disease after taking Q901. However, detailed safety information from these trials continues to be gathered and shared.

Pembrolizumab, also known as Keytruda, is already approved for certain types of cancer. Past studies have safely combined it with other treatments, demonstrating its general safety.

The current trial examines the safety and tolerability of using these treatments together. Although trying new treatment combinations can be concerning, pembrolizumab's prior approval and use with other treatments provide some confidence about its safety in a clinical setting. Nonetheless, ongoing research is necessary to fully understand the safety of using these treatments together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Q901 because it targets CDK7, a protein involved in the growth and division of cancer cells, offering a novel approach compared to current treatments like chemotherapy and targeted therapies that focus on other mechanisms. CDK7 inhibition could potentially slow or stop tumor growth more effectively by directly interfering with the cancer cell cycle. Additionally, when combined with pembrolizumab (KEYTRUDA®), an immune checkpoint inhibitor, Q901 may enhance the body's immune response against cancer, providing a powerful one-two punch against tumors. This novel mechanism and combination approach offer hope for more effective cancer treatments.

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

Research has shown that the CDK7 inhibitor Q901 may help treat certain cancers. In early studies, some patients experienced halted cancer growth, and one patient with pancreatic cancer showed partial improvement, with a noticeable drop in a cancer marker. Additionally, lab tests demonstrated that Q901 combined with another treatment led to significant tumor shrinkage.

In this trial, some participants will receive Q901 combined with pembrolizumab. Previous studies with pembrolizumab and other drugs have indicated that patients with various cancers lived longer. Pembrolizumab alone has proven effective for some cancers, such as head and neck cancer. These findings suggest that the combination of Q901 and pembrolizumab might effectively fight cancer. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults with certain advanced cancers (like ovarian, prostate, breast, endometrial, colorectal, lung or pancreatic) that have worsened after standard treatments or have no beneficial standard treatment available. They should be relatively active and able to care for themselves (ECOG status 0-2), expect to live at least 3 more months and must sign a consent form.

Inclusion Criteria

My cancer has worsened after standard treatment or there's no beneficial standard treatment available.

Life expectancy of at least 3 months

Signed, written IRB-approved informed consent form

Exclusion Criteria

Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of >470 msec (females) and >450 msec (males)

I have not had serious heart problems or a heart attack in the last 6 months.

I do not have any ongoing serious infections needing treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive Q901 in a dose-escalation study to determine safety, tolerability, and pharmacokinetics

8-12 weeks

Dose Expansion

Participants receive Q901 at the recommended phase 2 dose (RP2D) to evaluate safety and potential antitumor activity

12-16 weeks

Combination Treatment

Participants receive Q901 in combination with pembrolizumab to evaluate safety and potential antitumor activity

12-16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• Q901

Trial Overview The trial is testing Q901 alone and in combination with Pembrolizumab on various advanced solid tumors. It's an early-phase study to find the right dose based on safety and how well patients tolerate it while also looking for signs of tumor shrinkage.

How Is the Trial Designed?

Group I: Q901 Single-Agent Expansion Cohorts Experimental Treatment 1 Intervention

Group II: Q901 + KEYTRUDA® (pembrolizumab) Cohorts Experimental Treatment 2 Interventions

Group III: Dose escalation (Q901) Experimental Treatment 1 Intervention

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?

Qurient Co., Ltd.

Lead Sponsor

Trials

10

Recruited

840+

Merck Sharp & Dohme LLC

Industry 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

Published Research Related to This Trial

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, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

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]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

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]

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) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3078

A first-in-human trial of selective CDK7 inhibitor Q901 ... 2 patients at 18 mg/m2 and 2 patients at 36 mg/m2 had stable disease. Additional safety and efficacy data will be presented. Conclusions: ...

2. asco.org asco.org/abstracts-presentations/ABSTRACT456232

A first-in-human trial of selective CDK7 inhibitor Q901 ... 1 patient with pancreatic cancer who received 18 mg/m2 had a partial response with CA19-9 reduction from 4,632 to 219. 2 patients at 18 mg/m2 and 2 patients at ...

3. aacrjournals.org aacrjournals.org/cancerres/article/83/7_Supplement/5977/719373/Abstract-5977-Evaluation-of-the-potential

Evaluation of the potential combination regimens for q901, a ... In the MCF7 model, SERD alone showed 64% TGI and Q901 combination with SERD showed 94% TGI. Remarkable tumor regression (111% TGI) was observed ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05394103

NCT05394103 | Highly Selective CDK7 Inhibitor Q901 in ... The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome ...

5. researchgate.net researchgate.net/publication/381494972_A_first-in-human_trial_of_selective_CDK7_inhibitor_Q901_in_patients_with_advanced_solid_tumors_Interim_results_of_a_phase_I_study_QRNT-009

Interim results of a phase I study (QRNT-009). | Request PDF Results: As of data cutoff (12Jan2024), 17 patients received Q901 across 3 dose levels: 5 patients at 18 mg/m ² , 4 patients at 36 mg/m ² , and 8 patients at 60 ...

6. abmole.com abmole.com/literature/q901-msds.html?srsltid=AfmBOoqMtheJ7hwfQ8ok6NczvBJbPXbORacpgo_5bpmgCSIQQ2poTd_r

Material Safety Data Sheet of Q901 Material Safety Data Sheet of Q901 contains identification of substance and details of the supplier of the safety data sheet.

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)02735-7/fulltext

712TiP A phase I/II multicenter, open-label, dose- ... This phase 1/2 multicenter, open-label study (NCT05394103) evaluates the safety, pharmacodynamics, and pharmacokinetics of Q901 in adult patients with solid ...