ASP1570 + Pembrolizumab for Advanced Cancer

Recruiting at 46 trial locations

Overseen By Astellas Pharma Global Development Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Astellas Pharma Global Development, Inc.

Must not be taking: CYP2D6 inhibitors, Steroids

Disqualifiers: Autoimmune disease, CNS metastases, others

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

Compensation: Varies

Number of Visits: 3140

366 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment called ASP1570, alone or with other medicines like pembrolizumab, to see if it can help the immune system fight advanced cancers. Researchers seek to determine the safety and tolerability of ASP1570 and identify the best dose. This trial targets adults with advanced solid tumors that have worsened after standard treatments or who cannot receive those treatments. Participants should have a tumor that has spread beyond its original site or to other parts of the body. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

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

Research shows that ASP1570, when used alone, is generally safe, allowing most patients to take it without major problems. Early signs suggest that ASP1570 may help fight cancer, encouraging further research.

Pembrolizumab has received FDA approval to treat several types of cancer, proving safe and effective for many patients. However, specific safety information for using ASP1570 and pembrolizumab together is not yet available. Combining treatments can sometimes cause new side effects, so researchers will closely monitor participants for any issues.

These studies are in the early stages, with researchers still learning about possible side effects and the best dose. As a result, safety information is still being collected. Participants will be monitored carefully to ensure their safety throughout the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ASP1570 because it offers a new approach to treating advanced cancers, including non-small cell lung cancer (NSCLC) and microsatellite stable colorectal cancer (MSS-CRC). Unlike traditional options like chemotherapy, ASP1570 is being tested both alone and in combination with other treatments, such as pembrolizumab, which is an immunotherapy drug that helps the immune system attack cancer cells. One standout feature of ASP1570 is its potential for flexible dosing, like its stepwise escalation and intermittent dosing, which allows for personalized treatment plans. Additionally, combining ASP1570 with other agents, like docetaxel for NSCLC or TAS-102 and bevacizumab for MSS-CRC, could enhance treatment effectiveness by targeting cancer from multiple angles.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors?

Research shows that ASP1570 is designed to help the immune system fight cancer by reactivating T-cells, which are white blood cells that attack tumors. In this trial, some participants will receive ASP1570 with pembrolizumab, known to boost the immune system in various cancers, potentially enhancing the treatment's effectiveness. Early studies of ASP1570 alone have shown promising results, and it is being further tested for its effectiveness against advanced solid tumors. Other participants will receive ASP1570 combined with docetaxel, which has shown potential, especially for treating non-small cell lung cancer (NSCLC). Additionally, ASP1570 is being tested with TAS-102 and bevacizumab for colorectal cancer, aiming to improve outcomes. These combinations in the trial aim to tackle tumors that might resist single treatments, offering new hope for those with advanced cancers. ^{1 2 3 5 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ASP1570
• Pembrolizumab

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.

How Is the Trial Designed?

Group I: ASP1570 Monotherapy Dose Expansion NSCLC (Part 2) Experimental Treatment 1 Intervention

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

Group II: 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 III: 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 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 + Pembrolizumab + Pemetrexed + Carboplatin CTDE - NSCLC 1L (Part 2) Experimental Treatment 4 Interventions

Participants who have NSCLC will receive ASP1570 daily in a 21-day cycle. Pembrolizumab will be administered every 6 weeks on day 1 of every other ASP1570 cycle. Pemetrexed and carboplatin will be administered on day 1 of each 21-day cycle. Combination therapy Dose Expansion (CTDE)

Group X: 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.

Group XI: ASP1570 + Bevacizumab + mFOLFOX6 or FOLFIRI Combination therapy Dose Expansion - MSS-CRC 2L (Part 2) Experimental Treatment 6 Interventions

Participants who have MSS-CRC will receive ASP1570 in a 14-day cycle. Bevacizumab, will be administered every 2 weeks. mFOLFOX6 (oxaliplatin, Leucovorin, 5-fluorouracil) or FOLFIRI (Leucovorin, 5-Fluorouracil, Irinotecan) will administered every 2 weeks.

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

Published Research Related to This Trial

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) 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]

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 (Keytruda) is an effective treatment for advanced melanoma, showing significant improvements in progression-free survival and overall response rates compared to ipilimumab and chemotherapy in clinical trials involving patients with varying treatment histories.

The drug has a manageable safety profile, with immune-related side effects that are generally reversible, making it a valuable option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab: A Review in Advanced Melanoma. Deeks, ED.[2022]

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) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

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. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

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]

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 (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]

Citations

1. aacrjournals.org aacrjournals.org/mct/article/24/6/884/762655/Enhanced-Antitumor-Immunity-by-ASP1570-a-Novel

Enhanced Antitumor Immunity by ASP1570, a Novel ... The antitumor efficacy of ASP1570 was canceled by CD8+ T-cell depletion, indicating that its antitumor effect depends on CD8+ cytotoxic T-cell activation.

2. clinicaltrials.eu clinicaltrials.eu/inn/asp1570/

Asp1570 – Application in Therapy and Current Clinical ... The trials aim to evaluate the safety, tolerability, and effectiveness of ASP1570 in patients with various types of advanced solid tumors, offering hope for new ...

3. digitalcommons.providence.org digitalcommons.providence.org/publications/9729/

Phase 1/2 Trial of ASP1570, a Novel Diacylglycerol Kinase ... ASP1570 monotherapy had an acceptable safety profile and showed early signs of clinical activity, supporting further evaluation in patients with advanced solid ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02582-1/fulltext

1004P Phase I/II trial of ASP1570, a novel diacylglycerol ... The primary endpoint was safety; secondary endpoints were efficacy, pharmacokinetics (PK), and biomarker analysis. Blood and tumor biopsies were used for ...

5. clinicaltrials.astellas.com clinicaltrials.astellas.com/study/1570-CL-0101

A Study of ASP1570 taken by itself, or ... This study will provide more information on ASP1570 in adults with advanced solid tumors. ASP1570 will either be given by itself, or given with another medicine ...

6. jitc.bmj.com jitc.bmj.com/content/10/Suppl_2/A786

754 A phase 1/2 study of ASP1570 in participants with ... This is a phase 1/2, open-label, multicenter, multiple-dose, dose-escalation/expansion study of ASP1570 in participants with locally advanced or metastatic ...