NM1F + Pembrolizumab for Advanced Breast Cancer

Recruiting at 1 trial location

Overseen By Hang Zhou, Bachelor

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hefei TG ImmunoPharma Co., Ltd.

Must not be taking: Steroids, Immunosuppressants, Live vaccines

Disqualifiers: CNS tumors, Infections, Autoimmune, Cardiovascular, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1-2 years

38 Participants Needed

Trial Summary

What is the purpose of this trial?

A Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Antitumor Activity of NM1F as Monotherapy and in Combination with Pembrolizumab in Subjects with Locally Advanced/Metastatic Solid Tumors

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had certain cancer treatments or immunosuppressive drugs recently, so it's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug pembrolizumab for treating advanced breast cancer?

Pembrolizumab, also known as Keytruda, has been shown to improve survival rates and response rates in patients with advanced melanoma and non-small cell lung cancer, suggesting it may have potential benefits for other advanced cancers like breast cancer. ^{1 2 3 4 5}

Is the combination of NM1F and Pembrolizumab safe for humans?

Pembrolizumab, also known as Keytruda, 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 thyroid problems. While specific safety data for NM1F is not provided, pembrolizumab's safety profile is well-documented in other conditions. ^{5 6 7 8 9}

What makes the drug NM1F + Pembrolizumab unique for advanced breast cancer?

The combination of NM1F and Pembrolizumab is unique because it targets two different immune checkpoints, potentially enhancing the immune system's ability to fight advanced breast cancer. Pembrolizumab blocks the PD-1 protein, while NM1F targets PVRIG, a novel pathway, which may offer a new approach compared to existing treatments. ^{1 2 10 11 12}

Eligibility Criteria

This trial is for adults with advanced solid tumors, like colorectal or breast cancer, who've tried all standard treatments without success or can't tolerate them. They must be in a stable condition (ECOG PS 0~2), not pregnant, agree to use contraception, and have a life expectancy of at least 3 months.

Inclusion Criteria

My cancer is advanced, has spread, and doesn't respond to standard treatments.

I can take care of myself and am up and about more than half of my waking hours.

Female subjects of childbearing potential or male subjects with a partner of childbearing potential must agree to use effective contraception at the time of informed consent and continuing through the study until 6 months after the last dose of NM1F and / or pembrolizumab

Exclusion Criteria

I have a weak immune system due to conditions like SCID or frequent fluid build-ups needing drainage.

I have had a bone marrow or organ transplant.

I have a history of severe or ongoing infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive NM1F as monotherapy or in combination with pembrolizumab for dose escalation

1-2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term Follow-up

Participants are monitored for long-term outcomes such as overall survival and progression-free survival

Approximately 3 years

Treatment Details

Interventions

• NM1F Injection
• Pembrolizumab injection

Trial Overview The study tests NM1F alone and combined with Pembrolizumab on patients with advanced cancers. It's the first time humans are trying NM1F to see how safe it is, what side effects it has, and if it works against tumors.

Participant Groups

Group I: NM1F Injection/pembrolizumab Injection Experimental Treatment 2 Interventions

NM1F monotherapy dose escalation(Phase 1a) NM1F dose escalation in combination with a fixed dose of pembrolizumab(Phase 1b)

Who Is Running the Clinical Trial?

Hefei TG ImmunoPharma Co., Ltd.

Lead Sponsor

Trials

2

Recruited

160+

Findings from Research

In a long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., 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]

In a study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab and pemetrexed-carboplatin (PC) significantly improved the objective response rate (56.7% vs. 30.2% with PC alone) and progression-free survival (PFS) compared to PC alone, with a hazard ratio (HR) of 0.53.

The updated analysis showed a favorable overall survival (OS) hazard ratio of 0.56 for the pembrolizumab plus PC group, indicating a significant survival benefit, although 41% of patients experienced grade 3 to 5 treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. Borghaei, H., Langer, CJ., Gadgeel, S., et al.[2022]

Pembrolizumab (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[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 (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]

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 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 (Keytruda) is the first anti-PD-1 therapy approved in the US for treating advanced malignant melanoma, specifically for patients who have progressed after prior treatments.

It is designed to target the PD-1 protein, enhancing the immune system's ability to fight cancer, and is currently under review for approval in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. Poole, RM.[2021]

Pembrolizumab significantly improves progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) in patients with advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, based on a meta-analysis of 7 randomized controlled trials involving 3988 patients.

While pembrolizumab does not increase the frequency of common adverse events, it is associated with a higher occurrence of immune-related adverse events (irAEs), indicating a need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab for treating advanced non-small-cell lung cancer: a meta-analysis of phase II and III randomized controlled trials. Gong, T., Liu, L., Liu, Y., 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]

References

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

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]

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

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. [2022]

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

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

6. England pubmed.ncbi.nlm.nih.gov

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

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

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

8. 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]

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

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

10. New Zealand pubmed.ncbi.nlm.nih.gov

Pembrolizumab: first global approval. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of pembrolizumab for treating advanced non-small-cell lung cancer: a meta-analysis of phase II and III randomized controlled trials. [2022]

12. United States 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. [2021]