NP-G2-044 Monotherapy/Combination for Cancer

Recruiting at 15 trial locations

Overseen By Eszter Kotai

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Novita Pharmaceuticals, Inc.

Must be taking: Anti-PD-1 therapy

Must not be taking: Investigational agents, Immunosuppressants

Disqualifiers: Brain metastases, Heart failure, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 months

140 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called NP-G2-044, which may work alone or with another drug that helps the immune system fight cancer. It targets patients with severe, spreading cancers. The new drug might stop tumor growth and help the body's defenses fight cancer more effectively.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you are on certain investigational agents or require strong inhibitors or inducers of specific enzymes. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug NP-G2-044 Monotherapy/Combination for Cancer?

Research shows that PD-1 inhibitors, like pembrolizumab, improve survival in non-small-cell lung cancer patients with high PD-L1 expression. Combining PD-1 inhibitors with other treatments, such as chemotherapy, may further extend survival in patients who have progressed on PD-1 inhibitor monotherapy. ^{1 2 3 4 5}

What safety data exists for NP-G2-044 and similar treatments?

PD-1 and PD-L1 inhibitors, which are similar to NP-G2-044, have been shown to cause immune-related side effects, which can sometimes be serious. These side effects can include skin and mucosal reactions, and in rare cases, severe inflammation. It's important to monitor and manage these side effects to ensure safety during treatment. ^{6 7 8 9 10}

What makes NP-G2-044 Monotherapy/Combination for Cancer unique compared to other cancer treatments?

NP-G2-044 Monotherapy/Combination is unique because it combines NP-G2-044 with PD-1 inhibitors, which are known to block a pathway that tumors use to evade the immune system, potentially enhancing the body's ability to fight cancer. ^{1 11 12 13 14}

Research Team

Jillian Zhang, Ph.D.

Principal Investigator

Novita Pharmaceuticals, Inc.

Eligibility Criteria

Adults over 18 with advanced solid tumors, able to swallow pills and with good organ/bone marrow function. Women of childbearing age must test negative for pregnancy; men and women must use effective contraception. Excludes those with recent significant GI issues, brain metastases, heart problems, or who've had certain transplants or treatments recently.

Inclusion Criteria

Able to understand and voluntarily sign a written informed consent form and willing and able to comply with protocol requirements

I am 18 years old or older.

My blood, liver, and kidney functions are within normal ranges.

Exclusion Criteria

I haven't had chemotherapy or radiotherapy in the last 4 weeks.

I have side effects from cancer treatment that are not severe.

I am currently on medication to suppress my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NP-G2-044 monotherapy or combination therapy with anti-PD-1 therapy in 28-day cycles

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue treatment if showing benefit and tolerating therapy

Long-term

Treatment Details

Interventions

• Anti-PD-1 Therapy
• Anti-PD-(L)1 Therapy
• NP-G2-044 Combination therapy
• NP-G2-044 Monotherapy

Trial Overview The trial is testing NP-G2-044 alone and combined with anti-PD-1 therapy in patients with advanced solid tumors. It aims to assess safety, tolerability, initial effectiveness against the tumor, how the body processes the drug (pharmacokinetics), and its action on the body (pharmacodynamics).

Participant Groups

Group I: NP-G2-044 Monotherapy - Capsule/Tablet Experimental Treatment 1 Intervention

NP-G2-044 capsule/tablet PO QD for each 28-day cycle

Group II: NP-G2-044 Combination Therapy With Anti-PD-1 Therapy Experimental Treatment 2 Interventions

NP-G2-044 capsules PO QD for each 28-day cycle, Anti-PD-1 Therapy per standard of care, at a dose and frequency in accordance with the package insert

Anti-PD-1 Therapy is already approved in United States, European Union, China for the following indications:

Approved in United States as Pembrolizumab (Keytruda) for:

• Melanoma
• Non-small cell lung cancer
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Endometrial cancer

Approved in United States as Nivolumab (Opdivo) for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Squamous cell carcinoma of the head and neck
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma

Approved in European Union as Pembrolizumab (Keytruda) for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Urothelial carcinoma
• Head and neck squamous cell carcinoma
• Hodgkin lymphoma
• Colorectal cancer

Approved in European Union as Nivolumab (Opdivo) for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Squamous cell carcinoma of the head and neck
• Urothelial carcinoma
• Colorectal cancer

Approved in United States as Cemiplimab (Libtayo) for:

• Cutaneous squamous cell carcinoma
• Non-small cell lung cancer

Approved in China as Toripalimab (Loqtorzi) for:

• Melanoma
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in United States as Toripalimab (Loqtorzi) for:

• Nasopharyngeal carcinoma

Who Is Running the Clinical Trial?

Novita Pharmaceuticals, Inc.

Lead Sponsor

Trials

2

Recruited

160+

Findings from Research

In a study of 84 patients with advanced non-small-cell lung cancer (NSCLC), the use of PD-1 inhibitor monotherapy resulted in a longer progression-free survival (PFS) compared to PD-1 inhibitor plus chemotherapy, with median PFS of 9.6 months versus 4.6 months, respectively.

Despite the differences in PFS, the overall survival (OS) and disease control rate (DCR) were similar between the two treatment groups, and the incidence of adverse events was not significantly different, indicating that both treatment strategies are comparably safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes for PD-1 Inhibitor Plus Chemotherapy as Second-Line or Later Therapy Compared to PD-1/PD-L1 Inhibitor Alone in Advanced Non-small-cell Lung Cancer. Zhai, X., Jing, X., Li, J., et al.[2022]

In a study involving 51 patients with advanced non-small-cell lung cancer (NSCLC) who had previously undergone multiple treatments, the combination of pembrolizumab and ipilimumab demonstrated an objective response rate of 30%, indicating some level of antitumor activity.

While the combination therapy showed potential benefits, it also resulted in significant toxicity, with 64% of patients experiencing treatment-related adverse events, highlighting the need for careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with ipilimumab as second-line or later therapy for advanced non-small-cell lung cancer: KEYNOTE-021 cohorts D and H. Gubens, MA., Sequist, LV., Stevenson, JP., et al.[2020]

In a study of 187 patients with non-small-cell lung cancer (NSCLC) and PD-L1 expression of ≥50%, those with PD-L1 levels of 90%-100% showed significantly better treatment outcomes with pembrolizumab, including a higher overall response rate (60% vs. 32.7%) and longer median progression-free survival (14.5 months vs. 4.1 months).

Patients with higher PD-L1 expression not only had improved response rates but also longer overall survival, indicating that PD-L1 levels can be a critical factor in predicting the efficacy of pembrolizumab as a first-line treatment for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Aguilar, EJ., Ricciuti, B., Gainor, JF., et al.[2023]

In a phase II study involving 98 patients with non-small cell lung cancer (NSCLC) who had progressed on PD-1/PD-L1 inhibitors, adding pembrolizumab to chemotherapy did not significantly improve progression-free survival (PFS) or overall survival compared to placebo with chemotherapy.

However, in a subgroup of patients with high PD-L1 expression (≥50%) and favorable responses to prior treatment, those receiving pembrolizumab with chemotherapy had a higher 24-month survival rate, suggesting potential benefits in specific patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuation of Pembrolizumab with Additional Chemotherapy after Progression with PD-1/PD-L1 Inhibitor Monotherapy in Patients with Advanced NSCLC: A Randomized, Placebo-Controlled Phase II Study. Jung, HA., Park, S., Choi, YL., et al.[2023]

In a meta-analysis of 27 randomized controlled trials involving 15,590 patients with advanced non-small cell lung cancer, treatment effect sizes for progression-free survival (PFS) and overall survival (OS) were found to be comparable, suggesting that PFS can be a reliable endpoint in clinical trials.

However, the analysis indicated that PFS may not be as reliable for trials using immunotherapy as a second-line treatment, highlighting the need for caution when interpreting PFS data without OS outcomes in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in treatment effect size between progression-free survival and overall survival in anti-PD-1/PD-L1 inhibitors-based trials in advanced NSCLC: a systematic review and meta-analysis. Zhou, Z., Ren, S., Chen, L., et al.[2022]

In a meta-analysis of 11,465 patients from 18 clinical trials, PD-1/PD-L1 inhibitors were found to significantly increase the risk of developing dermatologic adverse effects like rash and pruritus compared to chemotherapy, with relative risks of 1.84 and 3.74, respectively.

PD-1/PD-L1 inhibitors showed a lower risk of mucosal inflammation and alopecia compared to chemotherapy, indicating a distinct safety profile that differs from traditional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. Yang, W., Li, S., Yang, Q.[2021]

Immune checkpoint inhibitors like ipilimumab and nivolumab can lead to a wide range of immune-related adverse events (irAEs), some of which may not be clinically apparent but can cause significant organ damage, as demonstrated in an autopsy of a 35-year-old female patient with metastatic melanoma.

The autopsy revealed severe systemic inflammation and damage in multiple organs, including the heart and central nervous system, highlighting the need for increased awareness and monitoring of irAEs in patients undergoing immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic inflammation in a melanoma patient treated with immune checkpoint inhibitors-an autopsy study. Koelzer, VH., Rothschild, SI., Zihler, D., et al.[2022]

A retrospective review of adverse events reported to the FDA revealed that PD-1 and PD-L1 inhibitors are associated with an increased risk of tuberculosis (TB) and atypical mycobacterial infection (AMI), with 72 cases of TB and 13 cases of AMI identified among users of these drugs.

The risk of developing TB was found to be 1.79 times higher and the risk of AMI was 5.49 times higher in patients treated with PD-1/PD-L1 inhibitors compared to other FDA-approved drugs, indicating that while these therapies can be effective for cancer, they carry significant risks that clinicians should monitor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mycobacterial infections due to PD-1 and PD-L1 checkpoint inhibitors. Anand, K., Sahu, G., Burns, E., et al.[2021]

In a review of 26 studies involving 3607 patients, the combination of PD-L1 inhibitors with CTLA-4 inhibitors resulted in a lower incidence of all-grade adverse events (67%) compared to the combination of PD-1 inhibitors with CTLA-4 inhibitors (89%).

This suggests that using PD-L1 inhibitors in combination therapy may offer a safer option with fewer treatment-related side effects than PD-1 inhibitors when paired with CTLA-4 inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors in clinical trials: a meta-analysis. Mi, Z., Zhang, Y., Feng, Z., et al.[2022]

Immune checkpoint antibodies targeting the PD-1/PD-L1 pathway have shown significant antitumor activity and have been approved for use as single-agent therapies in metastatic malignant melanoma and nonsmall-cell lung cancer.

Understanding the toxicities associated with PD-1/PD-L1 blockade and having effective management strategies is crucial for maximizing both the safety and efficacy of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Naidoo, J., Page, DB., Li, BT., et al.[2023]

The PD-1 pathway is crucial in helping tumors evade the immune system, and blocking this pathway can improve the body's immune response against cancers like advanced renal cell carcinoma and prostate cancer.

The review highlights the clinical effectiveness and safety profiles of anti-PD-L1 and anti-PD-1 antibodies, specifically BMS-936559, MK-3475, and BMS-936558, in enhancing antitumor activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed death 1 pathway inhibition in metastatic renal cell cancer and prostate cancer. Tang, PA., Heng, DY.[2021]

In the phase 3 MYSTIC trial involving 1118 patients with metastatic non-small cell lung cancer, durvalumab did not significantly improve overall survival compared to chemotherapy, nor did the combination of durvalumab and tremelimumab show better outcomes than chemotherapy for patients with high PD-L1 expression.

However, patients with a blood tumor mutational burden (bTMB) of 20 or more mutations per megabase experienced significantly improved overall survival with durvalumab plus tremelimumab, suggesting that bTMB may be a useful biomarker for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial. Rizvi, NA., Cho, BC., Reinmuth, N., et al.[2021]

Nivolumab therapy can lead to thyroid dysfunction, specifically painless thyroiditis, with thyrotoxicosis occurring within four weeks of treatment initiation in some patients, and subsequent hypothyroidism developing in others.

The study found that PD-L1 and PD-L2 are expressed in normal thyroid tissue, suggesting that nivolumab may disrupt immune tolerance in the thyroid, leading to thyroiditis and necessitating careful monitoring and management of thyroid function during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Features of Nivolumab-Induced Thyroiditis: A Case Series Study. Yamauchi, I., Sakane, Y., Fukuda, Y., et al.[2022]

Nivolumab, a PD-1 immune checkpoint inhibitor, has been approved for treating advanced non-small cell lung cancer (NSCLC) in multiple regions, including the US, Europe, and Asia.

This review specifically examines the efficacy and safety of nivolumab in NSCLC patients in Japan, highlighting its potential as a promising treatment option for this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for the treatment of Japanese patients with advanced metastatic non-small cell lung cancer: a review of clinical trial evidence for efficacy and safety. Hida, T.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Outcomes for PD-1 Inhibitor Plus Chemotherapy as Second-Line or Later Therapy Compared to PD-1/PD-L1 Inhibitor Alone in Advanced Non-small-cell Lung Cancer. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Pembrolizumab in combination with ipilimumab as second-line or later therapy for advanced non-small-cell lung cancer: KEYNOTE-021 cohorts D and H. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. [2023]

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

Continuation of Pembrolizumab with Additional Chemotherapy after Progression with PD-1/PD-L1 Inhibitor Monotherapy in Patients with Advanced NSCLC: A Randomized, Placebo-Controlled Phase II Study. [2023]

5. China pubmed.ncbi.nlm.nih.gov

Differences in treatment effect size between progression-free survival and overall survival in anti-PD-1/PD-L1 inhibitors-based trials in advanced NSCLC: a systematic review and meta-analysis. [2022]

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

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Systemic inflammation in a melanoma patient treated with immune checkpoint inhibitors-an autopsy study. [2022]

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

Mycobacterial infections due to PD-1 and PD-L1 checkpoint inhibitors. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors in clinical trials: a meta-analysis. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. [2023]

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

Programmed death 1 pathway inhibition in metastatic renal cell cancer and prostate cancer. [2021]

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

Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial. [2021]

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

Clinical Features of Nivolumab-Induced Thyroiditis: A Case Series Study. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Nivolumab for the treatment of Japanese patients with advanced metastatic non-small cell lung cancer: a review of clinical trial evidence for efficacy and safety. [2019]