Penpulimab for Nasopharyngeal Cancer

Not currently recruiting at 59 trial locations

Overseen By Zhifang Yao, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Akeso

Must not be taking: Immunotherapy, Corticosteroids, Immunosuppressants, others

Disqualifiers: Other malignancies, Autoimmune disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new treatment called penpulimab (an immunotherapy drug) when combined with chemotherapy for nasopharyngeal cancer. Researchers seek to determine if this combination outperforms a placebo (a non-active substance) with chemotherapy. Individuals with nasopharyngeal cancer that has spread or recurred after treatment, and who have not received other treatments for it, may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it excludes those who have had recent investigational drug treatments or certain medical conditions. It's best to discuss your specific medications with the trial investigators.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that penpulimab is likely to be safe for humans?

Research shows that penpulimab is generally well-tolerated by patients with nasopharyngeal cancer. Studies have found that this treatment, already approved by the FDA for certain types of nasopharyngeal cancer, is safe for most people, meaning they do not experience severe side effects.

Earlier research demonstrated that penpulimab effectively shrinks tumors with manageable side effects, even in patients who had tried several other treatments. This suggests it is a relatively safe option for people with this type of cancer.

For those considering joining a trial with penpulimab, this information might be reassuring. However, like any medical treatment, some side effects may occur, so discussing these with a healthcare provider is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Penpulimab is unique because it is an anti-PD-1 monoclonal antibody specifically designed to target and block the PD-1 pathway, potentially enhancing the immune system’s ability to fight nasopharyngeal cancer. Unlike standard treatments that primarily focus on chemotherapy agents like cisplatin, carboplatin, and gemcitabine, Penpulimab offers a novel mechanism of action by helping the immune system recognize and attack cancer cells more effectively. Researchers are excited about this treatment because it could lead to improved outcomes for patients by potentially increasing the effectiveness of existing chemotherapy regimens without adding significant toxicity.

What evidence suggests that penpulimab might be an effective treatment for nasopharyngeal cancer?

Research shows that penpulimab, an anti-PD-1 antibody, has promising effects in treating nasopharyngeal cancer, especially in patients who have tried several other treatments. In this trial, participants in Group A will receive penpulimab combined with cisplatin/carboplatin and gemcitabine. Studies have found that combining penpulimab with other drugs like gemcitabine has led to good results in managing this cancer. The FDA has approved penpulimab for treating a specific type of nasopharyngeal cancer, supporting its effectiveness. Additionally, research suggests that combining penpulimab with chemotherapy may help control cancer growth. These findings indicate that penpulimab can be an effective option for treating nasopharyngeal cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Xiaozhong Chen

Principal Investigator

Cancer Hospital of The University of Chinese Academy of Sciences

Chaosu Hu, MD

Principal Investigator

Fudan University

Are You a Good Fit for This Trial?

Adults aged 18-75 with recurrent or metastatic nasopharyngeal carcinoma, who haven't had systemic treatment for this condition and are not suitable for local therapy. They should have a life expectancy of at least 3 months, an ECOG performance status of 0 or 1 (meaning they are fully active or restricted in physically strenuous activity but can do light work), and adequate organ function. Participants must be willing to use effective contraception.

Inclusion Criteria

At least one measurable lesion according to RECIST v1.1

My cancer diagnosis is nasopharyngeal carcinoma.

I have nasopharyngeal cancer that has spread and cannot be treated locally, or it came back 6 months after treatment.

Exclusion Criteria

Participation in treatment with an investigational drug or use of an investigational device within 4 weeks before first study dosing

I have received immunotherapy for my cancer before.

Pregnant or nursing (lactating) women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive penpulimab or placebo combined with chemotherapy (cisplatin/carboplatin and gemcitabine) for the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and overall survival

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Penpulimab

Trial Overview The trial is testing Penpulimab combined with chemotherapy versus a placebo combined with chemotherapy in patients with nasopharyngeal carcinoma. It's randomized (participants are assigned by chance) and double-blind (neither the researchers nor participants know who gets which treatment).

How Is the Trial Designed?

Group I: Group A Experimental Treatment 1 Intervention

Group A (study group): Penpulimab plus cisplatin/carboplatin and gemcitabine

Group II: Group B Placebo Group 1 Intervention

Group B (control group): Placebo plus cisplatin/carboplatin and gemcitabine

Penpulimab is already approved in China for the following indications:

Approved in China as Penpulimab for:

• Classic Hodgkin’s lymphoma
• Locally advanced or metastatic squamous non-small cell lung cancer
• Nasopharyngeal carcinoma

Who Is Running the Clinical Trial?

Akeso

Lead Sponsor

Trials

122

Recruited

23,400+

Dr. Simon Williams

Akeso

Chief Executive Officer since 2022

PhD in Organic Chemistry from Cambridge University

Dr. Baiyong Li

Akeso

Chief Medical Officer

MD from an unspecified institution

Published Research Related to This Trial

In a study of 203 patients with recurrent or metastatic nasopharyngeal carcinoma, the combination of anti-EGFR antibody and chemotherapy resulted in a median overall survival of 29.1 months and a progression-free survival of 8.9 months, indicating promising antitumor activity.

The treatment was generally well-tolerated, with leukopenia being the most common adverse event, affecting 84.2% of patients, suggesting that while there are side effects, the combination therapy is manageable and warrants further investigation in randomized clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-epidermal growth factor receptor monoclonal antibody plus palliative chemotherapy as a first-line treatment for recurrent or metastatic nasopharyngeal carcinoma. Chen, C., Zhou, Y., Zhang, X., et al.[2021]

Penpulimab is a humanized anti-PD-1 monoclonal antibody that has been engineered to enhance anti-tumor activity by eliminating Fcγ receptor binding, which can interfere with its effectiveness.

In August 2021, penpulimab was approved in China for treating adult patients with relapsed or refractory classic Hodgkin's lymphoma after at least second-line chemotherapy, and it is currently under review for other cancers like nasopharyngeal cancer and non-small cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Penpulimab: First Approval. Dhillon, S.[2022]

In a study of 128 advanced nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT), the NFP chemotherapy regimen (nedaplatin plus fluorouracil and paclitaxel) showed superior 5-year overall survival (88.5% vs. 75.4%) and distant metastasis-free survival (89.0% vs. 75.1%) compared to the NP regimen (nedaplatin plus paclitaxel).

While the NFP group had better survival outcomes, it also experienced a higher incidence of severe acute toxicities, including significant bone marrow suppression and liver and renal dysfunction, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma. Yin, L., Bian, XH., Wang, X., et al.[2019]

In a study of 50 patients with locally advanced nasopharyngeal carcinoma, concurrent chemoradiotherapy using carboplatin followed by carboplatin and 5-fluorouracil resulted in a 100% objective response rate for the primary tumor, with 92% achieving a complete response.

The treatment demonstrated a favorable 3-year overall survival rate of 89.7% and a progression-free survival rate of 72.7%, with manageable toxicities primarily including weight loss and mucositis, indicating good tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiotherapy with carboplatin followed by carboplatin and 5-fluorouracil in locally advanced nasopharyngeal carcinoma. Dechaphunkul, T., Pruegsanusak, K., Sangthawan, D., et al.[2021]

In a study of 307 patients with locally advanced nasopharyngeal carcinoma, adding nimotuzumab (NTZ) to concurrent chemoradiotherapy significantly improved the 5-year overall survival rate (94.1% vs. 81.8%) and disease-free survival rate (84.2% vs. 75.5%) compared to chemoradiotherapy alone.

While NTZ improved treatment efficacy, it was associated with increased risks of severe hematologic toxicity and acute oral mucositis, highlighting the need for careful monitoring of side effects in patients receiving this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and survival analysis of nimotuzumab combined with concurrent chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma. Wang, L., Zhuang, H., Xu, X., et al.[2023]

In a meta-analysis of four randomized clinical trials, the combination of PD-1 inhibitors with chemotherapy significantly improved overall survival (OS) in patients with recurrent or metastatic nasopharyngeal carcinoma compared to chemotherapy alone, with a hazard ratio of 0.64 (p=0.01).

Patients receiving the combination therapy also showed better progression-free survival (PFS) and objective response rates, indicating that adding PD-1 inhibitors enhances treatment efficacy in this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive PD-1 inhibitor versus standard chemotherapy in recurrent or metastatic nasopharyngeal carcinoma: a systematic review and meta-analysis. Polintan, ET., Canicula, SK., Catahay, JA., et al.[2022]

In a phase 2 trial involving 33 patients with metastatic nasopharyngeal carcinoma (mNPC) who had previously failed platinum-based chemotherapy, the combination of sintilimab and bevacizumab showed a promising objective response rate (ORR) of 54.5%, indicating significant antitumor activity.

The treatment was generally well-tolerated, with manageable side effects; the most common adverse event was mild hypothyroidism, and no treatment-related deaths were reported, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of sintilimab plus bevacizumab in metastatic nasopharyngeal carcinoma after failure of platinum-based chemotherapy: an open-label phase 2 study. Lu, N., Jiang, YF., Xia, WX., et al.[2023]

In a study of 6078 nasopharyngeal cancer patients, those who used Metformin had a significantly lower risk of death from cancer compared to non-users, with an adjusted hazard ratio of 0.80.

The findings suggest that Metformin could be a beneficial addition to standard treatment regimens for nasopharyngeal cancer, highlighting the need for further randomized control trials to confirm its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association between Metformin and the Cancer-Specific Mortality Rate in Nasopharyngeal Cancer Patients: Real-World Evidence. Hsu, Y., Hsu, CY., Kao, YS.[2023]

In a phase II trial involving 25 patients with recurrent nasopharyngeal carcinoma, toripalimab combined with intensity-modulated radiotherapy (IMRT) resulted in a high overall response rate of 79.2% and disease control in 95.8% of patients at 3 months post-treatment.

The treatment was found to be tolerable, with low incidences of severe acute side effects, although some patients experienced late severe complications such as nasopharyngeal wall necrosis (28.0%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: an open-label single-arm, phase II trial. Hua, Y., You, R., Wang, Z., et al.[2022]

In a phase II study involving 190 patients with recurrent or metastatic nasopharyngeal carcinoma (NPC), the PD-1 inhibitor toripalimab showed an objective response rate (ORR) of 20.5%, with a median duration of response of 12.8 months, indicating its potential efficacy in this challenging patient population.

A significant correlation was found between a ≥ 50% decrease in plasma Epstein-Barr virus (EBV) DNA after 28 days of treatment and a better response to toripalimab, with an ORR of 48.3% in these patients, suggesting that monitoring EBV levels could help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02). Wang, FH., Wei, XL., Feng, J., et al.[2023]

In a study of 67 patients with recurrent and metastatic nasopharyngeal carcinoma, combining anti-PD1 checkpoint inhibitors with chemotherapy resulted in a significantly higher objective response rate (ORR) of 53.8% compared to 14.6% for anti-PD1 alone.

The combination therapy also led to improved progression-free survival (PFS) and overall survival (OS) at 6 months, with rates of 65.4% and 100.0% respectively, compared to 28.6% and 73.5% for the anti-PD1 only group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-PD1 checkpoint inhibitor with or without chemotherapy for patients with recurrent and metastatic nasopharyngeal carcinoma. Jin, T., Zhang, Q., Jin, QF., et al.[2021]

A meta-analysis of 23 studies showed that adding cetuximab to conventional treatment for nasopharyngeal carcinoma (NPC) significantly improves treatment efficacy, leading to higher response rates and prolonged survival.

While cetuximab enhances treatment outcomes, it is associated with increased skin toxicity, suggesting that monitoring skin reactions could help guide its use in NPC therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination treatment with cetuximab in advanced nasopharyngeal carcinoma patients: a meta-analysis. Shen, J., Sun, C., Zhou, M., et al.[2022]

Citations

1. nature.com nature.com/articles/s41392-024-01865-6

Penpulimab, an anti-PD-1 antibody, for heavily pretreated ... Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04974398

NCT04974398 | A Study of Penpulimab (AK105) in the First ... Expected survival of ≥ 3 months. Histologically or cytologically confirmed nasopharyngeal carcinoma. Subjects with primary metastatic (nasopharyngeal carcinoma, ...

3. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-penpulimab-kcqx-non-keratinizing-nasopharyngeal-carcinoma

FDA approves penpulimab-kcqx for non-keratinizing ... FDA approves penpulimab-kcqx for non-keratinizing nasopharyngeal carcinoma ... The primary efficacy outcome measure was progression-free ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6040

Long-term outcomes of anlotinib and penpulimab ... The long term outcomes of this phase 2 study preliminarily disclosed the advantage of the treatment regimen including gemcitabine, anlotinib and penpulimab as ...

5. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT011/761700/Abstract-CT011-Penpulimab-versus-placebo-in

Abstract CT011: Penpulimab versus placebo in combination ... This presentation reports the results of a global phase 3 clinical trial with ethnically diverse patients treated with penpulimab plus ...

6. akesobio.com akesobio.com/en/media/akeso-news/250425

Akeso Announces FDA Approval for Penpulimab-kcqx in ... These studies demonstrated the drug's clinical benefits and favorable safety profile across two stages of treatment for metastatic NPC. AK105- ...