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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for cervical cancer that has returned or spread, particularly in patients whose cancer no longer responds to pembrolizumab (an immunotherapy drug). The trial compares pembrolizumab alone with a new combination of PRGN-2009 (a type of immunotherapy) plus pembrolizumab to determine which is more effective and safe. Patients with recurring or spreading cervical cancer, who have previously tried pembrolizumab without success, and whose tumors test positive for specific markers (PD-L1 and HPV16/18) may be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research has shown that using PRGN-2009 with pembrolizumab yields promising safety results. Earlier studies found that PRGN-2009, when combined with a checkpoint inhibitor (a drug that helps the immune system fight cancer), achieved a 30% success rate in patients with HPV-related cancers who had already received multiple treatments. This indicates the treatment was effective and generally well-tolerated.

Pembrolizumab is already approved for treating several types of cancer, and its safety is well-established. It is commonly used and generally considered safe when administered alone.

In summary, both PRGN-2009 and pembrolizumab have demonstrated good safety records in earlier studies. While each treatment can have side effects, the evidence so far suggests that this combination is generally well-tolerated in patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PRGN-2009 combined with Pembrolizumab for cervical cancer because this combination offers a novel approach by targeting the cancer with both an immune checkpoint inhibitor and a therapeutic vaccine. While Pembrolizumab helps the immune system recognize and attack cancer cells, PRGN-2009 is a vaccine designed to further stimulate an immune response specifically against tumors. This dual action could potentially enhance the effectiveness of treatment compared to using Pembrolizumab alone, offering hope for better outcomes in cervical cancer patients.

What evidence suggests that this trial's treatments could be effective for cervical cancer?

This trial will compare two treatment approaches for cervical cancer: Pembrolizumab alone and the combination of PRGN-2009 with Pembrolizumab. Research has shown that combining PRGN-2009 with Pembrolizumab may help treat cervical cancer. In an earlier study, this combination helped about 30% of patients with heavily treated HPV-related cancers, with nearly one in three patients experiencing a reduction or disappearance of their cancer. PRGN-2009 boosts the immune system to better target cancer cells. Pembrolizumab is already known to help the immune system attack cancer by removing its barriers. Together, these treatments might offer a new option for those whose cancer hasn't responded to other treatments. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. investors.precigen.com investors.precigen.com/news-releases/news-release-details/precigen-announces-positive-phase-1-data-shelf-prgn-2009

Press Releases PRGN-2009 combined with an investigational checkpoint inhibitor resulted in a 30% ORR in patients with heavily pre-treated HPV-associated cancers.

2. prnewswire.com prnewswire.com/news-releases/precigen-receives-fda-clearance-of-ind-to-initiate-phase-2-study-of-prgn-2009-off-the-shelf-adenoverse-immunotherapy-in-combination-with-pembrolizumab-to-treat-patients-with-recurrent-or-metastatic-cervical-cancer-301838033.html

Precigen Receives FDA Clearance of IND to Initiate Phase ... Phase 2 study of PRGN-2009 is in combination with pembrolizumab in the second line setting in patients with recurrent or metastatic cervical cancer.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06157151

Study Details | NCT06157151 | PRGN-2009 in ... This randomized trial will evaluate the efficacy and safety of PRGN-2009 in combination with pembrolizumab compared to pembrolizumab alone in patients with ...

4. sec.gov sec.gov/Archives/edgar/data/1356090/000095010324004017/dp208564_ex9901.htm

99.1 The Phase 2 randomized, open-label study of PRGN-2009 in combination with pembrolizumab in patients with HPV-associated recurrent/metastatic ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT05996523

Phase II Trial of Immunotherapeutic HPV Vaccine PRGN ... “PRGN-2009 in OPSCC and Cervical Cancer: An abstract titled, 'Phase II trial of immunotherapeutic HPV vaccine PRGN-2009 with pembrolizumab before standard ...

6. investors.precigen.com investors.precigen.com/news-releases/news-release-details/precigen-receives-fda-clearance-ind-initiate-phase-2-study-prgn

Precigen Receives FDA Clearance of IND to Initiate Phase ... Precigen Receives FDA Clearance of IND to Initiate Phase 2 Study of PRGN-2009 Off-the-Shelf AdenoVerse Immunotherapy in Combination with ...

7. prnewswire.com prnewswire.com/news-releases/precigen-announces-positive-phase-1-data-for-off-the-shelf-prgn-2009-adenoverse-immunotherapy-alone-and-in-combination-with-an-investigational-checkpoint-inhibitor-in-patients-with-recurrentmetastatic-hpv-associated-cancers-301841791.html

Precigen Announces Positive Phase 1 Data for Off-the- ... PRGN-2009 combined with an investigational checkpoint inhibitor resulted in a 30% ORR in patients with heavily pre-treated HPV-associated cancers.

8. firstwordpharma.com firstwordpharma.com/story/5838518

Precigen Reports Full Year 2023 Financial Results and Business ... PRGN-2009 in OPSCC and Cervical Cancer: PRGN-2009 is an investigational off-the-shelf AdenoVerse immunotherapy designed to activate the immune system to ...