NDI-101150 + Pembrolizumab for Cancer

Not currently recruiting at 21 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, NDI-101150 (an experimental treatment), alone or with pembrolizumab (an immunotherapy drug), for people with advanced solid tumors. The goal is to determine the right dose and assess the safety and early effects of the treatment. It suits those whose cancer no longer responds to standard treatments. Participants will receive either NDI-101150 pills alone or with pembrolizumab infusions. The study aims to evaluate how these treatments affect tumor growth and patient health. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that NDI-101150, when used alone, is generally well tolerated by patients with advanced solid tumors. In studies, common side effects were manageable. For instance, in a group of 29 patients with a type of kidney cancer, the treatment proved safe enough to continue.

When combined with pembrolizumab, a drug already approved for other cancers, early research suggests NDI-101150 might help reactivate important immune cells, even in challenging conditions. Although still under study, this combination has demonstrated a promising safety record in ongoing research.

These findings suggest that both NDI-101150 alone and with pembrolizumab are generally well-tolerated, with manageable side effects noted in the early stages of the studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NDI-101150 because it offers a fresh approach to cancer treatment by targeting specific pathways differently than current therapies. Unlike standard treatments that often involve chemotherapy or radiation, NDI-101150 is a targeted therapy taken orally, which could potentially offer a more convenient and less invasive option for patients. Additionally, when combined with pembrolizumab, an established immunotherapy, it could enhance the body's immune response against cancer cells, possibly leading to more effective results. The combination therapy's unique delivery method and mechanism of action make it a promising candidate in the fight against cancer.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research has shown that NDI-101150, one of the treatments in this trial, yields promising results when used alone for advanced solid tumors. In earlier studies, it helped 18% of patients with kidney cancer who had already tried many treatments. Another study found that 25% of patients responded to the treatment, with some experiencing complete or partial tumor shrinkage.

In this trial, another group of participants will receive a combination of NDI-101150 with pembrolizumab. This combination enhances the immune system's ability to fight tumors. Studies have found that it reactivates important immune cells, like T-cells and B-cells, even in situations where the immune response is usually weak. These findings suggest that both NDI-101150 alone and with pembrolizumab could help treat advanced cancers by strengthening the body's natural defenses. ^{1 3 4 6 7}

Who Is on the Research Team?

Anita Scheuber, MD

Principal Investigator

Nimbus Saturn

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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, 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]

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]

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) 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]

Citations

1. nimbustx.com nimbustx.com/2024/11/07/nimbus-therapeutics-presents-positive-updated-data-from-phase-1-2-clinical-trial-of-hpk1-inhibitor-for-advanced-solid-tumors-at-sitc-39th-annual-meeting/

Nimbus Therapeutics Presents Positive Updated Data from ... NDI-101150 monotherapy achieved 18% objective response rate in heavily pretreated renal cell carcinoma (RCC) patients with prior exposure to checkpoint ...

2. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.4537

Ongoing phase 1/2 trial of the hematopoietic progenitor ... Results: As of 20 November 2024, 106 patients were dosed [NDI-101150 monotherapy (n = 94) or NDI-101150 + pembrolizumab (n = 12)].

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40738502/

Highly selective HPK1 inhibitor NDI-101150 mediates ... Highly selective HPK1 inhibitor NDI-101150 mediates immune cell activation and robust antitumor responses, distinct from immune checkpoint ...

4. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A782

682 Ongoing phase 1/2 trial of the HPK1 inhibitor NDI- ... NDI-101150 demonstrated an overall response rate of 25%, which included a complete response in one patient at 50 mg and a partial response in another patient at ...

5. nimbustx.com nimbustx.com/wp-content/uploads/SITC24_Clinical-poster_NDI-101150_Final-23Oct2024.pdf

Ongoing Phase 1/2 Trial of the HPK1 Inhibitor NDI-101150 ... • We report here updated safety data in all dose cohorts and tumor types as well as efficacy data in patients with renal cell carcinoma (RCC) ...

6. onclive.com onclive.com/view/ndi-101150-demonstrates-antitumor-activity-safety-in-heavily-pretreated-rcc

NDI-101150 Demonstrates Antitumor Activity, Safety in ... NDI-101150 monotherapy demonstrated antitumor activity and was well tolerated among patients with heavily pretreated renal cell carcinoma.

7. ecancer.org ecancer.org/en/video/12415-hpk1-inhibitor-ndi-101150-shows-safety-and-antitumour-activity-in-ccrcc

HPK1 inhibitor NDI-101150 shows safety and antitumour ... Among 29 ccRCC patients treated with NDI-101150 monotherapy, the drug demonstrated a manageable safety profile with common adverse events ...