PRGN-2009 + Pembrolizumab for Cervical Cancer

Recruiting at 2 trial locations

Overseen By Amy Lankford

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Precigen, Inc

Must be taking: Pembrolizumab

Disqualifiers: Active malignancy, CNS disease, others

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2009

Duration: 1 year

46 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug pembrolizumab for cervical cancer?

Pembrolizumab has been approved by the FDA for use in patients with recurrent or metastatic cervical cancer whose tumors express PD-L1, based on a phase II trial showing a response rate of 14.3%. It has shown durable responses in patients with PD-L1-expressing cervical cancer, although its effectiveness is limited in a broader patient population. ^{1 2 3 4 5}

Is the combination of PRGN-2009 and Pembrolizumab safe for treating cervical cancer?

Pembrolizumab, also known as Keytruda, has been used in treating cervical cancer and other conditions, with some patients experiencing side effects like pneumonitis (lung inflammation) and other adverse events. In a study of cervical cancer patients, 47% experienced side effects, and 6.8% had severe reactions, including two suspected treatment-related deaths, so safety should be carefully monitored. ^{1 2 6 7 8}

What makes the PRGN-2009 + Pembrolizumab treatment unique for cervical cancer?

The PRGN-2009 + Pembrolizumab treatment is unique because it combines an immune checkpoint inhibitor, pembrolizumab, which targets the PD-1 receptor to help the immune system attack cancer cells, with PRGN-2009, a novel immunotherapy designed to enhance the immune response against cancer. This combination aims to improve outcomes in patients with cervical cancer, especially those whose tumors express PD-L1, compared to using pembrolizumab alone. ^{1 3 9 10 11}

What is the purpose of this trial?

This randomized trial will evaluate the efficacy and safety of PRGN-2009 in combination with pembrolizumab compared to pembrolizumab alone in patients with pembrolizumab-resistant recurrent or metastatic cervical cancer.

Eligibility Criteria

This trial is for adults over 18 with recurrent or metastatic cervical cancer resistant to pembrolizumab. Participants must have tried no more than two systemic treatments, have PD-L1 and HPV16/18 positive tumors, measurable disease, good performance status (ECOG 0 or 1), and a life expectancy of at least 12 weeks. Women must not be pregnant, agree to contraception use during the study and for six months after.

Inclusion Criteria

Negative serum pregnancy test. Women of child-bearing potential (WOCBP) must agree to use adequate contraception prior to study entry and for at least 6 months following completion of study treatment

I can understand and am willing to sign the consent form.

My cervical cancer has returned or spread and does not respond to pembrolizumab.

Exclusion Criteria

Pregnant and lactating women are excluded from this study

I have not had any other active cancer in the past year.

I have a diagnosed brain or spinal cord condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PRGN-2009 in combination with pembrolizumab or pembrolizumab alone

1 year

PRGN-2009: q3W for 3 administrations, then q6w; Pembrolizumab: q6w

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

Treatment Details

Interventions

• Pembrolizumab
• PRGN-2009

Trial Overview The trial compares PRGN-2009 combined with Pembrolizumab versus Pembrolizumab alone in patients whose cervical cancer has returned or spread despite previous treatment with Pembrolizumab. It aims to assess the effectiveness and safety of this new combination therapy.

Participant Groups

Group I: PRGN-2009 plus Pembrolizumab Experimental Treatment 1 Intervention

PRGN-2009 at a dose of 5 x 10\^11 PU q3W for 3 administrations, then q6w, plus Pembrolizumab, 400mg q6w

Group II: Pembrolizumab alone Active Control 1 Intervention

Pembrolizumab, 400mg q6w

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Precigen, Inc

Lead Sponsor

Trials

7

Recruited

300+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Pembrolizumab is an FDA-approved immune checkpoint inhibitor specifically targeting the PD-1 receptor, showing promise in treating recurrent or metastatic cervical cancer in patients whose tumors express PD-L1.

Clinical studies suggest that pembrolizumab could become a preferred treatment option for advanced cervical cancer, but further research is needed to identify which patients will benefit the most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced cervical cancer: safety and efficacy. De Felice, F., Giudice, E., Bolomini, G., et al.[2021]

Pembrolizumab, a PD-1 inhibitor, has been approved by the FDA as a second-line treatment for recurrent or metastatic cervical cancer in patients with a PD-L1 combined positive score of at least 1.

In a phase II trial, pembrolizumab demonstrated an objective response rate of 14.3%, indicating its potential efficacy in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab OK'd for Cervical Cancer. [2019]

Pembrolizumab, an antibody targeting the PD-1 receptor, has shown limited effectiveness as a standalone treatment for recurrent and/or metastatic cervical cancer in the general patient population, but it has received accelerated approval from the FDA for patients with PD-L1-expressing tumors due to its potential for durable responses.

Future research is focusing on combining pembrolizumab with other therapies like chemotherapy and radiotherapy, and identifying additional biomarkers beyond PD-L1 expression will be crucial to better select patients who are likely to benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of cervical cancer. Marret, G., Borcoman, E., Le Tourneau, C.[2020]

In a phase II study involving 98 patients with previously treated advanced cervical cancer, pembrolizumab showed an objective response rate (ORR) of 12.2%, with all responses occurring in patients with PD-L1-positive tumors, indicating its efficacy in this specific group.

The treatment was generally well-tolerated, with manageable safety profiles; 65.3% of patients experienced treatment-related adverse events, but only 12.2% had severe (grade 3 to 4) adverse events, leading to its accelerated approval by the FDA for advanced PD-L1-positive cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. Chung, HC., Ros, W., Delord, JP., et al.[2021]

In a study of 14 patients with advanced cervical cancer treated with pembrolizumab, the objective response rate was 21%, with a durable clinical benefit rate of 36%, indicating some patients experienced significant treatment effects.

Patients with metastatic disease limited to the lungs and/or lymph nodes showed improved responses to pembrolizumab, and those with a higher tumor mutational burden had better outcomes, suggesting these factors may help identify who will benefit most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pattern of disease and response to pembrolizumab in recurrent cervical cancer. Miller, KM., Filippova, OT., Hayes, SA., et al.[2022]

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]

In a study of 117 patients with recurrent cervical cancer treated with pembrolizumab, the overall response rate was 9.4%, with a higher response rate of 18.9% in patients with better performance status (ECOG ≤1).

While pembrolizumab demonstrated modest antitumor activity, safety concerns were noted, with 47% of patients experiencing adverse events, including two treatment-related deaths, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Experience of Pembrolizumab Monotherapy in Patients with Recurrent or Persistent Cervical Cancer: A Korean Multi-Center Retrospective Study (KGOG1041). Choi, MC., Kim, YM., Lee, JW., et al.[2020]

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]

In a study of 11 heavily pretreated patients with recurrent cervical cancer, pembrolizumab demonstrated a clinical benefit rate of 36%, with 18% of patients showing a partial response and another 18% achieving disease stabilization.

The treatment was generally well tolerated, with a median overall survival of 26 weeks and a 6-month survival rate of 65%, indicating promising efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of Pembrolizumab in Recurrent Cervical Cancer: Case Series and Review of Published Data. Kranawetter, M., Röhrich, S., Müllauer, L., et al.[2019]

A study involving 29 cervical carcinoma cases assessed the interobserver agreement among 5 experienced pathologists interpreting PD-L1 expression, showing a high consensus rate of 90% for determining eligibility for pembrolizumab treatment.

Pure squamous cell carcinomas were consistently classified as PD-L1 positive, while tumors with glandular components had a significant rate of negative consensus, indicating that tumor histology can influence PD-L1 scoring and patient selection for immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interobserver Agreement on the Interpretation of Programmed Death-ligand 1 (PD-L1) Combined Positive Score (CPS) Among Gynecologic Pathologists. Mills, AM., Bennett, JA., Banet, N., et al.[2023]

A patient with advanced, chemo-refractory uterine cervical small cell carcinoma experienced a significant reduction in liver metastases after treatment with a tumor vaccine combined with pembrolizumab, indicating potential efficacy of this combination therapy.

This case highlights the aggressive nature of this rare cancer and suggests that immunotherapy, specifically pembrolizumab, may offer a new treatment avenue, although further research is needed to establish standardized therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A transient increase and subsequent sharp decrease of chemo-refractory liver-metastasized uterine cervical small cell carcinoma to autologous formalin-fixed tumor vaccine plus anti-PD-1 antibody. Miyoshi, T., Kataoka, T., Asahi, A., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced cervical cancer: safety and efficacy. [2021]

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

Pembrolizumab OK'd for Cervical Cancer. [2019]

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

Pembrolizumab for the treatment of cervical cancer. [2020]

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

Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Pattern of disease and response to pembrolizumab in recurrent cervical cancer. [2022]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Real-World Experience of Pembrolizumab Monotherapy in Patients with Recurrent or Persistent Cervical Cancer: A Korean Multi-Center Retrospective Study (KGOG1041). [2020]

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. England pubmed.ncbi.nlm.nih.gov

Activity of Pembrolizumab in Recurrent Cervical Cancer: Case Series and Review of Published Data. [2019]

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

Interobserver Agreement on the Interpretation of Programmed Death-ligand 1 (PD-L1) Combined Positive Score (CPS) Among Gynecologic Pathologists. [2023]

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

A transient increase and subsequent sharp decrease of chemo-refractory liver-metastasized uterine cervical small cell carcinoma to autologous formalin-fixed tumor vaccine plus anti-PD-1 antibody. [2022]