NDI-101150 + Pembrolizumab for Cancer

Recruiting at 19 trial locations

Overseen By Study Coordinator

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 1 & 2

Sponsor: Nimbus Saturn, Inc.

Must not be taking: Steroids, CYP3A4/CYP2C8 inducers

Disqualifiers: Transplant, CNS disease, cardiovascular, others

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

Compensation: Varies

Number of Visits: 1

106 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called NDI-101150, alone or with pembrolizumab, in adults with advanced cancers. It aims to find the safest dose and see how well it works. Pembrolizumab helps the immune system attack cancer cells and is used to treat various cancers.

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

The trial requires that you stop taking any medications that strongly affect certain liver enzymes (CYP3A4 and CYP2C8). If you're on such medications, you would need to discontinue them before participating.

What data supports the effectiveness of the drug pembrolizumab for cancer treatment?

Pembrolizumab has shown effectiveness in treating various cancers, including non-small cell lung cancer (NSCLC) and melanoma, by improving survival rates and being well-tolerated. It works by helping the immune system recognize and attack cancer cells. ^{1 2 3 4 5}

Is the combination of NDI-101150 and Pembrolizumab safe for humans?

Pembrolizumab (also known as Keytruda or MK-3475) has been used in various cancer treatments and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and more serious immune-related issues like pneumonitis (lung inflammation) and colitis (inflammation of the colon). While specific safety data for the combination with NDI-101150 is not provided, pembrolizumab's safety profile is well-documented in other conditions. ^{1 2 6 7 8}

How is the drug NDI-101150 + Pembrolizumab unique for cancer treatment?

The combination of NDI-101150 with pembrolizumab (Keytruda) is unique because it pairs a novel treatment (NDI-101150) with pembrolizumab, a PD-1 inhibitor that helps the immune system recognize and attack cancer cells. This combination may offer a new approach for cancers that have not responded well to existing treatments. ^{1 2 3 7 9}

Research Team

Anita Scheuber, MD

Principal Investigator

Nimbus Saturn

Eligibility Criteria

This trial is for adults with advanced solid tumors who have a life expectancy of at least 12 weeks, are willing to undergo tumor biopsies if needed, and have recovered from previous therapies. They should not have had cancer treatment in the last 4 weeks and must be in good physical condition (ECOG status 0-1). People with recent malignancies, severe allergies to monoclonal antibodies, untreated brain cancers, significant heart or lung conditions, or uncontrolled medical issues cannot join.

Inclusion Criteria

My bone marrow, kidney, and liver are functioning well.

My cancer can be measured by scans for the treatment study.

I agree to a tumor biopsy and have advanced cancer with no standard treatment options.

Exclusion Criteria

I do not have any severe uncontrolled health conditions.

I have a brain or spinal cord tumor that hasn't been treated, is spreading, or needs medication.

I have a serious heart condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Dose Escalation

Evaluate the safety and tolerability of NDI-101150 as monotherapy and in combination with pembrolizumab

Variable, based on disease progression or other criteria

Dose Expansion

Evaluate the safety and efficacy of NDI-101150 in disease-specific cohorts

Variable, based on disease progression or other criteria

Follow-up

Participants are monitored for safety and effectiveness after treatment

Until lost to follow-up, withdrawal of consent, or end of study

Treatment Details

Interventions

• NDI-101150
• Pembrolizumab

Trial Overview The study aims to find the safest high dose (MTD) and best Phase 2 dose (RP2D) of NDI-101150 alone or combined with pembrolizumab. It will look into how these treatments affect patients' bodies (pharmacokinetics), their action on tumors (pharmacodynamics), safety profiles, and initial effectiveness against solid tumors.

Participant Groups

Group I: NDI-101150-Pembrolizumab (Combination therapy) Experimental Treatment 2 Interventions

Patients in escalation and expansion phase, will receive NDI-101150 capsules orally once daily continuously in 3-week cycles (21 days), along with pembrolizumab via intravenous (IV) infusion at a dose of 200 mg every 3 weeks.

Group II: NDI-101150 (Monotherapy) Experimental Treatment 1 Intervention

Patients in escalation and expansion, will receive NDI-101150 capsules orally once daily continuously in 4-week cycles (28 days).

Who Is Running the Clinical Trial?

Nimbus Saturn, Inc.

Lead Sponsor

Trials

1

Recruited

110+

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, 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]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

The KEYNOTE-001 trial demonstrated that pembrolizumab significantly improves clinical outcomes for patients with advanced non-small cell lung cancer, indicating its efficacy as a treatment option.

Patients whose tumors express PD-L1 in at least 50% of cells showed better responses to pembrolizumab, suggesting that PD-L1 expression is a key factor in predicting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Shows Promise for NSCLC. [2015]

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 (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) has been approved by the FDA for treating high-risk, non-muscle invasive bladder cancer (NMIBC) in patients who are unresponsive to BCG therapy and are either ineligible for or have opted not to undergo cystectomy.

This approval specifically targets patients with carcinoma in situ (CIS) with or without papillary tumors, highlighting its role as a treatment option for those with limited surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. Wright, KM.[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 (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]

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. England pubmed.ncbi.nlm.nih.gov

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

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

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022]

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

Pembrolizumab Shows Promise for NSCLC. [2015]

5. 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]

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 Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]