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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for advanced breast cancer that cannot be removed by surgery. Researchers aim to determine the safety and effectiveness of combining NM1F (an experimental treatment) with pembrolizumab (an injection) for these patients. They seek individuals whose cancer has worsened despite standard treatments or who cannot tolerate them. Participants should have at least one measurable tumor to assess the treatment's response. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

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

Research shows that NM1F remains in the early stages of human testing, so information about its safety is limited. In the Phase 1 trial, the main goal is to assess its safety and tolerability. This trial will identify any side effects.

Pembrolizumab, in contrast, is more familiar and already used for other conditions. Studies have shown it can be safe, but like many treatments, it may cause side effects. Common ones include fatigue, nausea, and itching. Serious side effects are less common but possible.

Overall, while pembrolizumab has a known safety record, NM1F is newer, and the trial aims to better understand its safety. Participants should be aware of potential risks and discuss them with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about NM1F combined with pembrolizumab for advanced breast cancer because it represents a novel approach to treatment. Unlike traditional therapies that primarily target cancer cells directly, NM1F works by enhancing the body's immune response, potentially improving the effectiveness of pembrolizumab, an established immunotherapy. This combination aims to boost the body's natural defenses more robustly, offering new hope for patients with advanced stages of breast cancer where current options might fall short.

What evidence suggests that NM1F and pembrolizumab could be effective for advanced breast cancer?

Research shows that pembrolizumab effectively treats advanced triple-negative breast cancer. Studies found that adding pembrolizumab to chemotherapy extended the time patients lived without their cancer worsening. On average, patients using pembrolizumab and chemotherapy lived for 23 months.

This trial studies NM1F both as a monotherapy and in combination with pembrolizumab. Early research suggests NM1F might enhance the immune system's ability to fight tumors by targeting a protein that allows tumors to evade detection. Although more research is needed, combining NM1F with pembrolizumab in this trial could enhance treatment effectiveness because they complement each other. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 (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 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 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 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 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 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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05746897

Study Details | NCT05746897 | A First-in-human, Phase I ... This is a Phase 1, multicenter, open-label, two-parts, FIH study to evaluate the tolerability, safety, PK/PD, and preliminary anti-tumor activity of NM1F.

2. trials.braintumor.org trials.braintumor.org/trials/NCT05746897

A First-in-human, Phase I, Open-label, Multicenter Study of NM1F ... Search Results. A First-in-human, Phase I, Open-label, Multicenter Study of NM1F(Anti-PVRIG) in Patients With Advanced Solid Tumors. Study Purpose.

3. withpower.com withpower.com/trial/phase-1-triple-negative-breast-neoplasms-2-2023-8a100

NM1F + Pembrolizumab for Advanced Breast Cancer Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10981589/

Characterization of a novel anti-PVRIG antibody with Fc- ... Taken together, these data suggest that targeting PVRIG may augment the immune response and achieve optimal antitumor efficacy. Currently, ...

5. targetedonc.com targetedonc.com/view/study-explores-anti-pvrig-therapy-plus-nivolumab-and-anti-tigit-therapy-in-advanced-solid-tumors

Study Explores Anti-PVRIG Therapy Plus Nivolumab and ... The study excludes patients with advanced solid tumors who have active autoimmune disease requiring systemic treatment, symptomatic interstitial ...

6. data.niaid.nih.gov data.niaid.nih.gov/resources?id=9787

A First-in-human, Phase I, Open-label, Multicenter Study of ... A Phase 1 Study to Investigate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Antitumor Activity of NM1F as Monotherapy and in Combination ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e14695

Phase I safety and preliminary efficacy of PM1009, a ... Phase I safety and preliminary efficacy of PM1009, a bispecific antibody targeting TIGIT and PVRIG, in patients with advanced solid tumors.