ASP1570 + Pembrolizumab for Advanced Cancer

Recruiting in Palo Alto (17 mi)

+18 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Astellas Pharma Global Development, Inc.

Must not be taking: CYP2D6 inhibitors, Steroids

Disqualifiers: Autoimmune disease, CNS metastases, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing ASP1570, a new drug that helps the immune system fight cancer by reactivating T-cells. It targets adults with advanced solid tumors that have spread and are not responding to standard treatments. ASP1570 works by counteracting the signals that tumors use to turn off T-cells. The study will determine the best dose and test its effectiveness alone or with another drug called pembrolizumab.

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain medications before starting the study. Specifically, any previous cancer treatments must be stopped at least 21 days before the first dose of the study drug, except for some specific therapies that can be continued until 4 days before. It's best to discuss your current medications with the study doctor to understand what changes might be needed.

What data supports the effectiveness of the drug pembrolizumab in treating advanced cancer?

Pembrolizumab has shown effectiveness in treating various cancers, including non-small cell lung cancer and advanced melanoma, by improving survival rates and slowing disease progression. It works by helping the immune system attack cancer cells more effectively. ^{1 2 3 4 5}

Is the combination of ASP1570 and Pembrolizumab safe for humans?

Pembrolizumab (also known as KEYTRUDA or MK-3475) has been used in various clinical trials for different cancers, showing some common side effects like fatigue, cough, nausea, and rash. More serious immune-related side effects can include lung inflammation, liver inflammation, and thyroid issues. While these studies provide safety data for Pembrolizumab, specific safety information for the combination with ASP1570 is not available in the provided research. ^{1 2 3 6 7}

What makes the drug ASP1570 + Pembrolizumab unique for advanced cancer?

The combination of ASP1570 with Pembrolizumab is unique because it pairs a novel treatment (ASP1570) with Pembrolizumab, a well-established drug that enhances the immune system's ability to fight cancer by blocking the PD-1 pathway, which is a mechanism tumors use to evade immune detection. This combination aims to improve the effectiveness of cancer treatment by leveraging the strengths of both components. ^{1 2 3 8 9}

Research Team

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Eligibility Criteria

Adults with advanced solid tumors, including NSCLC or melanoma, who have worsened after standard therapy or can't receive it. They must have at least one measurable tumor lesion and be in good physical condition (ECOG 0-1). Participants should not have had recent major surgery, known allergies to the drugs being tested, uncontrolled illnesses, certain infections like HIV/HBV/HCV, or received other treatments that could interfere with the trial.

Inclusion Criteria

My side effects from previous treatments have mostly gone away.

My lung cancer does not have mutations like EGFR, ALK, or NTRK.

My condition worsened after standard treatments, or I can't or won't use them.

Exclusion Criteria

I have a history of unusual bleeding.

I am allergic to ASP1570 or pembrolizumab.

I have taken steroids or other immune-weakening medicines in the last 14 days.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Dose escalation to determine the most suitable dose of ASP1570, administered alone or in combination with pembrolizumab or standard cancer therapies

21-day cycles

Daily dosing with ASP1570, pembrolizumab every 6 weeks

Treatment Part 2

Dose expansion using the most suitable dose of ASP1570 determined from Part 1, with specific therapies for different tumor types

21-day or 28-day cycles

Daily dosing with ASP1570, pembrolizumab every 6 weeks, other therapies as per label

Follow-up

Participants are monitored for safety and effectiveness after treatment

45 days after end of treatment

Treatment Details

Interventions

• ASP1570 (Other)
• Pembrolizumab (Checkpoint Inhibitor)

Trial Overview The study tests ASP1570 alone or combined with pembrolizumab on adults with advanced solid tumors. Part 1 determines the best dose of ASP1570; participants take increasing doses unless significant issues arise. In Part 2, they continue with the established best dose from Part 1. Pembrolizumab is given every six weeks for some patients.

Participant Groups

Group I: ASP1570 Monotherapy Dose Expansion Microsatellite stable - colorectal cancer (MSS-CRC) (Part 2) Experimental Treatment 1 Intervention

Participants who have MSS-CRC will receive ASP1570 in a 21-day cycle.

Group II: ASP1570 Monotherapy Dose Expansion - Stepwise dosing (Part 2) Experimental Treatment 1 Intervention

Participants will receive ASP1570 administered by intra-subject dose escalation with gradual multiple dose steps (e.g., 3 steps) and increased dose up to RP2D in a 21-day cycle. This cohort will be opened at the discretion of the sponsor.

Group III: ASP1570 Monotherapy Dose Expansion - Prophylactic (Part 2) Experimental Treatment 1 Intervention

Participants will receive RP2D of ASP1570 along with the standard prophylactic medication in a 21-day cycle. This cohort will be opened at the discretion of the sponsor.

Group IV: ASP1570 Monotherapy Dose Expansion - Intermittent dosing (Part 2) Experimental Treatment 1 Intervention

Participants will receive RP2D of ASP1570 with some periodical drug holiday in a 21-day cycle. This cohort will be opened at the discretion of the sponsor.

Group V: ASP1570 Monotherapy Dose Expansion - Food Effect (Part 2) Experimental Treatment 1 Intervention

Participants will receive RP2D of ASP1570 after the meal in a 21-day cycle. This cohort will be opened at the discretion of the sponsor.

Group VI: ASP1570 Monotherapy Dose Escalation (Part 1) Experimental Treatment 1 Intervention

Participants will receive daily dose of ASP1570 in a 21-day cycle.

Group VII: ASP1570 + pembrolizumab Combination therapy Dose Escalation (Part 1) Experimental Treatment 2 Interventions

Participants will receive daily dose of ASP1570 in a 21-day cycle. pembrolizumab will be administered every 6 weeks on day 1 of every other ASP1570 cycle.

Group VIII: ASP1570 + TAS-102 + Bevacizumab Combination therapy Dose Expansion - MSS-CRC 3L+ (Part 2) Experimental Treatment 3 Interventions

Participants who have MSS-CRC will receive ASP1570 daily in a 28-day cycle. TAS-102 (Trifluridine + Tipiracil) will be administered on days 1 through 5 and days 8 through 12 of each 28-day cycle. Bevacizumab will be administered every 2 weeks.

Group IX: ASP1570 + Docetaxel Combination therapy Dose Expansion - NSCLC 2L+ (Part 2) Experimental Treatment 2 Interventions

Participants who have NSCLC will receive RP2D of ASP1570 daily in a 21-day cycle. Docetaxel will be administered every 6 weeks on day 1 of every other ASP1570 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

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (Keytruda) was approved by the FDA for treating metastatic non-small cell lung cancer (mNSCLC) in patients with tumors expressing PD-L1, showing significant improvements in overall survival (OS) and progression-free survival (PFS) in two major clinical trials with thousands of participants.

In the KEYNOTE-024 trial, pembrolizumab demonstrated a 40% reduction in the risk of death compared to chemotherapy, while in the KEYNOTE-010 trial, it also showed a significant survival advantage over chemotherapy in patients who had previously progressed on treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. Pai-Scherf, L., Blumenthal, GM., Li, H., et al.[2022]

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 long-term study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab with pemetrexed-carboplatin significantly improved the objective response rate (58% vs. 33%) and progression-free survival (24.5 months vs. 9.9 months) compared to chemotherapy alone.

Patients who completed 2 years of pembrolizumab treatment had a remarkable 92% survival rate at the data cutoff, indicating a durable clinical benefit, while the safety profile remained manageable with no new safety concerns identified.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. Awad, MM., Gadgeel, SM., Borghaei, H., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) is an approved treatment for metastatic or locally advanced esophageal and gastroesophageal junction cancer, indicating its efficacy in targeting these specific cancer types.

It is used in combination with platinum- and fluoropyrimidine-based chemotherapy, suggesting a synergistic approach to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. Aschenbrenner, DS.[2023]

References

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

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]

3. 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]

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

Pembrolizumab: A Review in Advanced Melanoma. [2022]

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

Long-Term Overall Survival From KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin With or Without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous NSCLC. [2021]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

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

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

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]

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

Pembrolizumab Approved for Esophageal or Gastroesophageal Cancer. [2023]