ASP1012 + Pembrolizumab for Cancer

Recruiting at 4 trial locations

Overseen By Astellas Pharma Global Development, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Astellas Pharma Global Development, Inc.

Must not be taking: Corticosteroids, Immunosuppressives, Antivirals, others

Disqualifiers: Autoimmune disorders, CNS metastases, HIV, others

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

Compensation: Varies

Number of Visits: 28

229 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that participants must comply with prohibited medication restrictions, so it's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug pembrolizumab in cancer treatment?

Research shows that pembrolizumab, a drug that helps the immune system fight cancer, improves survival in patients with advanced lung cancer and melanoma. It has been effective in patients with specific markers on their cancer cells, leading to longer life and better quality of life compared to traditional chemotherapy. ^{1 2 3 4 5}

Is the combination of ASP1012 and Pembrolizumab safe for humans?

Pembrolizumab, also known as KEYTRUDA or MK-3475, has been studied for safety in various cancers. It generally has a favorable safety profile, but there are rare serious side effects, including infections, heart issues, and lung inflammation. The risk of fatal adverse events is similar to chemotherapy, and it varies depending on the type of cancer and whether it is combined with other treatments. ^{5 6 7 8 9}

What makes the drug ASP1012 + Pembrolizumab unique for cancer treatment?

The combination of ASP1012 with Pembrolizumab is unique because it aims to enhance the immune system's ability to fight cancer by combining Pembrolizumab, a well-established immune checkpoint inhibitor, with ASP1012, which may have a novel mechanism or target. This combination could potentially improve outcomes in cancers that are less responsive to Pembrolizumab alone. ^{8 10 11 12 13}

What is the purpose of this trial?

This trial tests ASP1012, a modified virus that targets and kills cancer cells, in adults with advanced or spreading tumors. The study aims to find a safe dose and check for side effects. ASP1012 helps the immune system recognize and fight cancer cells.

Research Team

Central Contact

Principal Investigator

Astellas Pharma Global Development, Inc.

Eligibility Criteria

Adults with advanced solid tumors that have grown or spread and who've tried all standard treatments can join. It's not for those with a specific skin cancer (acral lentiginous melanoma) or ovarian cancer patients in remission without measurable disease. Participants must have confirmed diagnoses, and some will need to show certain biomarkers.

Inclusion Criteria

I had Stage II-IV colon cancer, treated with surgery and chemotherapy, and have no visible cancer but positive for ctDNA.

I have had melanoma treatment with specific immunotherapies or targeted therapies if my melanoma has a BRAF mutation.

I have stage II-IV ovarian cancer in remission with a CA-125 level over 70 U/mL after standard treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants with locally advanced or metastatic tumors receive escalating doses of ASP1012 to determine suitable doses for further study parts.

Up to 28 days

Multiple visits (in-person)

Dose Expansion

Participants receive ASP1012 at doses determined from Dose Escalation phase, with or without pembrolizumab, depending on cancer type.

3 cycles of 21 days each

Clinic visits every 21 days, some virtual or by phone

Follow-up

Participants are monitored for safety and effectiveness after treatment, with clinic visits and phone follow-ups.

Up to 19 months

Clinic visits within 7 and 30 days post-treatment, phone follow-ups every 12 weeks

Treatment Details

Interventions

• ASP1012
• Pembrolizumab

Trial Overview ASP1012, an oncolytic virus designed to target and kill cancer cells while sparing healthy ones, is being tested alone or with pembrolizumab (an approved drug). The trial has three parts: dose finding, expanding the dose to more patients, and testing in specific cancers like stomach and colorectal.

Participant Groups

Group I: Part 3: ASP1012 Dose Expansion (previously treated gastric cancer) Experimental Treatment 1 Intervention

Participants with previously treated gastric cancer will receive ASP1012 with dose level selected from dose escalation (Part 1) in a 21-day cycle.

Group II: Part 3: ASP1012 Dose Expansion (ovarian cancer) Experimental Treatment 1 Intervention

Participants with ovarian cancer will receive ASP1012 with dose level selected from dose escalation (Part 1) in a 21-day cycle.

Group III: Part 3: ASP1012 Dose Expansion (other solid tumor type) Experimental Treatment 1 Intervention

Participants with other solid tumor type will receive ASP1012 with dose level selected from dose escalation (Part 1) in a 21-day cycle.

Group IV: Part 3: ASP1012 Dose Expansion (colorectal cancer [CRC]) Experimental Treatment 1 Intervention

Participants with CRC will receive ASP1012 with dose level selected from dose escalation (Part 1) in a 21-day cycle.

Group V: Part 2: ASP1012 Dose Expansion (Monotherapy) Experimental Treatment 1 Intervention

Participants with previously treated melanoma will receive ASP1012 with dose level(s) selected from dose escalation (Part 1) in a 21-day cycle.

Group VI: Part 2: ASP1012 + Pembrolizumab Dose Expansion (treatment-naïve melanoma) Experimental Treatment 2 Interventions

Participants with treatment-naïve melanoma will receive ASP1012 in a 21-day cycle. Pembrolizumab will also be administered every three weeks in a 21-day cycle, for up to 3 doses.

Group VII: Part 2: ASP1012 + Pembrolizumab Dose Expansion (previously treated solid tumors) Experimental Treatment 2 Interventions

Participants with previously treated solid tumors, will receive ASP1012 in a 21-day cycle. Pembrolizumab will also be administered every three weeks in a 21-day cycle, for up to 3 doses.

Group VIII: Part 1: ASP1012 Dose Escalation Experimental Treatment 1 Intervention

Participants with previously treated solid tumor types will receive ASP1012 in a 21-day cycle.

Who Is Running the Clinical Trial?

Astellas Pharma Global Development, Inc.

Lead Sponsor

Trials

204

Recruited

123,000+

Tadaaki Taniguchi

Astellas Pharma Global Development, Inc.

Chief Medical Officer

M.D., Ph.D.

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

Findings from Research

A 68-year-old patient with stage IV lung adenocarcinoma showed an unexpected positive response to paclitaxel after failing treatment with pembrolizumab, an anti-PD-1 immunotherapy.

The patient experienced a response duration of over fourteen months with paclitaxel, suggesting that combining or sequencing chemotherapy with immunotherapy may enhance treatment effectiveness in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. Zapata, E., Mennecier, B., Leduc, C., et al.[2017]

In a study involving 1274 patients with untreated metastatic non-small-cell lung cancer and a PD-L1 tumor proportion score (TPS) of 1% or greater, pembrolizumab monotherapy significantly improved overall survival compared to chemotherapy, with median survival times of 20.0 months versus 12.2 months for those with a TPS of 50% or greater.

Pembrolizumab also demonstrated a better safety profile, with only 18% of patients experiencing severe treatment-related adverse events compared to 41% in the chemotherapy group, suggesting it is a safer first-line treatment option for patients with low PD-L1 TPS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Mok, TSK., Wu, YL., Kudaba, I., et al.[2022]

Pembrolizumab is a monoclonal antibody that blocks the PD-1/PD-L1 interaction, which is crucial for preventing the immune system from attacking tumors, making it a key player in cancer immunotherapy.

It has been approved by the FDA for treating patients with advanced melanoma who have not responded to previous treatments, highlighting its efficacy in managing difficult cases of this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the management of advanced melanoma - role of pembrolizumab. Improta, G., Leone, I., Donia, M., et al.[2020]

In the KEYNOTE-024 study involving 305 patients with untreated advanced non-small-cell lung cancer, pembrolizumab significantly improved overall survival (OS) compared to platinum-based chemotherapy, with a median OS of 30.0 months versus 14.2 months for chemotherapy.

Pembrolizumab also had a better safety profile, with fewer treatment-related severe adverse events (31.2% for pembrolizumab vs. 53.3% for chemotherapy), indicating it is a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. Reck, M., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

In a phase 3 trial involving 305 patients with advanced non-small-cell lung cancer (NSCLC), pembrolizumab significantly improved quality of life (QOL) compared to chemotherapy, with a notable increase in the global health status score by 6.9 points versus a decrease of 0.9 points for chemotherapy.

Patients treated with pembrolizumab experienced a longer time to deterioration in symptoms like cough and chest pain, with 31% showing deterioration compared to 39% in the chemotherapy group, indicating that pembrolizumab may be a preferable first-line treatment for patients with PD-L1-positive NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. Brahmer, JR., Rodríguez-Abreu, D., Robinson, AG., et al.[2022]

Pembrolizumab, an anti-PD-1 antibody, has been approved for treating unresectable or metastatic melanoma, especially in patients who have progressed after ipilimumab treatment, marking a significant advancement in immuno-oncology.

The drug has also received breakthrough status for treating non-small cell lung cancer (NSCLC) that is EGFR mutation-negative and ALK rearrangement-negative, indicating its broad potential in cancer therapy, with ongoing trials to explore its use in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab. Khoja, L., Butler, MO., Kang, SP., et al.[2022]

In a study of 655 patients with advanced melanoma, pembrolizumab showed a 5-year overall survival rate of 34%, with even better outcomes (41%) for treatment-naive patients, indicating its long-term efficacy.

The treatment was generally well-tolerated, with 86% of patients experiencing treatment-related adverse events, but only 7.8% discontinued due to these effects, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. Hamid, O., Robert, C., Daud, A., et al.[2023]

Pembrolizumab is an effective monoclonal antibody that targets the PD-1 immune checkpoint, helping to restore T cell anti-tumor responses, and is administered at a dose of 200 mg every 3 weeks until disease progression or for up to 24 months.

It has received approval for treating various cancers, including melanomas and non-small cell lung cancers, particularly in tumors that are hypermutated or express PD-L1, but ongoing research aims to expand its use to less immunogenic tumor types through combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. du Rusquec, P., de Calbiac, O., Robert, M., et al.[2023]

In a meta-analysis of 11 clinical trials involving 3713 patients, the overall incidence of fatal adverse events (FAEs) associated with pembrolizumab was found to be 1.2%, indicating a relatively low risk of severe complications from this immune checkpoint inhibitor.

The incidence of FAEs varied significantly by tumor type, with breast cancer patients experiencing a higher risk (3.1%) compared to melanoma patients (0.2%), and the combination of pembrolizumab with chemotherapy resulted in a much higher incidence of FAEs (7.0%) compared to pembrolizumab alone (0.7%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatal Adverse Events Associated with Pembrolizumab in Cancer Patients: A Meta-Analysis. Sher, AF., Golshani, GM., Wu, S.[2020]

Pembrolizumab (PEM) significantly improved short-term treatment effectiveness and long-term survival rates in patients with advanced cutaneous malignant melanoma compared to chemotherapy with Temozolomide, with a notable increase in one-year survival rates (53.85% vs. 40.00%).

The use of PEM did not lead to a higher incidence of adverse reactions compared to the control group, indicating that it is a relatively safe treatment option for patients with this type of melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. Fu, L., Zhang, H., Jiang, J., et al.[2021]

A systematic review of four trials involving 3425 patients found that lower doses of pembrolizumab (2 mg/kg every 3 weeks) are equally effective as higher doses (10 mg/kg) in treating advanced melanoma and non-small-cell lung cancer (NSCLC).

The safety profile of pembrolizumab was similar across different doses, suggesting that the lower dose may be sufficient for routine treatment without compromising efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. Abdel-Rahman, O.[2018]

A study of 112 patients with non-small cell lung cancer (NSCLC) found that EBUS TBNA is effective for obtaining samples suitable for PD-L1 testing, with 82% of samples adequate for all ancillary tests.

The results showed a high satisfaction rate for PD-L1 expression testing, with 86% of cases yielding satisfactory results and 32% of patients exhibiting high PD-L1 expression levels (>50%), which is important for treatment decisions with pembrolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical performance of endobronchial ultrasound-guided transbronchial needle aspiration for assessing programmed death ligand-1 expression in nonsmall cell lung cancer. Biswas, A., Leon, ME., Drew, P., et al.[2018]

The ongoing KEYNOTE-495/KeyImPaCT study is evaluating the effectiveness of pembrolizumab combined with other therapies in advanced non-small cell lung cancer (NSCLC), with results showing varying objective response rates (ORR) based on tumor characteristics, ranging from 0-12% in low T-cell-inflamed groups to 50-60% in high T-cell-inflamed groups.

The study confirms that assessing T-cell-inflamed gene expression profiles (TcellinfGEP) and tumor mutational burden (TMB) can help identify which patients are more likely to benefit from pembrolizumab-based treatments, while the safety profiles of the combinations remain consistent with previous findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. Gutierrez, M., Lam, WS., Hellmann, MD., et al.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. [2017]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

New developments in the management of advanced melanoma - role of pembrolizumab. [2020]

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

Updated Analysis of KEYNOTE-024: Pembrolizumab Versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score of 50% or Greater. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life results for pembrolizumab versus chemotherapy in advanced, PD-L1-positive NSCLC (KEYNOTE-024): a multicentre, international, randomised, open-label phase 3 trial. [2022]

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

Pembrolizumab. [2022]

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

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001. [2023]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data. [2023]

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

Fatal Adverse Events Associated with Pembrolizumab in Cancer Patients: A Meta-Analysis. [2020]

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

Clinical application effect of Pembrolizumab in the treatment of advanced cutaneous malignant melanoma. [2021]

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

Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review. [2018]

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

Clinical performance of endobronchial ultrasound-guided transbronchial needle aspiration for assessing programmed death ligand-1 expression in nonsmall cell lung cancer. [2018]

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

Biomarker-directed, pembrolizumab-based combination therapy in non-small cell lung cancer: phase 2 KEYNOTE-495/KeyImPaCT trial interim results. [2023]