A Phase 1/2 Study of ASP1570 as Monotherapy and in Combination With Pembrolizumab or Standard Therapies Including Chemotherapy and/or Immunotherapy in Participants With Locally Advanced or Metastatic Solid Tumors
Immune therapies work with the body's immune system to treat a number of cancers. They work with T-cells, a type of white blood cell, to target and attack specific tumors. However, some tumors can become resistant to attack by T-cells over time. They do this by sending off signals to T-cells. The researchers are finding ways to switch the T-cells back on. Before a treatment can be approved for use, clinical studies need to be done. 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 called pembrolizumab, or given with a standard cancer therapy. The main aims of this study are： * To check the safety of ASP1570 * To check how well ASP1570 is tolerated * To find a suitable dose of ASP1570 This study is for adults with advanced solid tumors. Their tumor has either grown outside of the area where it started (locally advanced and unresectable) or it has spread to other parts of the body (metastatic). Their cancer gets worse after standard therapy or they are unable to have standard therapy. The study doctors can give more advice about who can take part. This study will be in 2 parts. In Part 1, the most suitable dose of ASP1570 to give to people with advanced solid tumors will be worked out. Different small groups of people with advanced solid tumors will take lower to higher doses of ASP1570. People will either be given ASP1570 by itself, ASP1570 with another medicine called pembrolizumab, or ASP1570 with a standard cancer therapy. The study treatment given depends on the type of cancer people have. There are different doses of ASP1570, with each group staying on the same dose. There is just 1 dose of pembrolizumab. The dose of a standard cancer therapy depends on its label. After taking the lowest dose of ASP1570, the first group will be checked for medical problems. The next group can only take the higher dose of ASP1570 if the first group tolerates the lowest dose . This will continue in the same way for each group. Each group will take tablets of ASP1570 either once or twice every day in a 21-day cycle. People taking part in Japan will stay in hospital for up to 21 days during the first treatment cycle only. People will continue with more treatment cycles on the same dose unless they can't tolerate the study treatment, their cancer gets worse or the study doctor decides that person should stop treatment. People who also receive treatment with pembrolizumab will be infused with pembrolizumab on the first day of every other cycle of ASP1570 (once every 6 weeks). People who are receiving standard cancer therapy (with ASP1570) will be treated according to its label. In Part 2, different small groups of people with advanced solid tumors will take the most suitable dose of ASP1570 worked out from Part 1. The dose will not go above the highest dose that people could tolerate from Part 1. Some groups of people will have specific advanced tumors. These include colorectal cancer or non-small cell lung cancer (NSCLC for short). Again, each group will take tablets of ASP1570 once or twice every day in a 21-day or 28-day cycle. People with NSCLC will also receive docetaxel, one of the standard cancer therapies. People with stable colorectal cancer (known as CRC with microsatellite stability, or MSS-CRC) will also receive another standard cancer therapy called TAS-102 with bevacizumab. The standard cancer therapies will be given according to their label. People with solid tumors will also receive pembrolizumab on the first day of every other cycle of ASP1570 (once every 6 weeks). All groups will continue with more treatment cycles with ASP1570 by itself with pembrolizumab, or with one of the standard cancer therapies unless they can't tolerate the study treatment, their cancer gets worse or the study doctor decides that person should stop treatment.
• Participant has locally-advanced (unresectable) or metastatic solid tumor malignancy which is confirmed by available pathology records or current biopsy.
• Participant has at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Monotherapy and Combination Escalation Cohorts and China-specific Safety Lead-in Cohort:
• a) Participant has progressed on standard therapies, is no longer eligible for standard therapies or has refused standard approved therapies (no limit to the number of prior treatment regimens). (UNIQUE to China: Tumor types will be determined at the sponsor's discretion.)
• Monotherapy Expansion Cohorts and China-specific Safety Lead-in Cohort:
• a) Participant has histologically confirmed diagnosis of locally advanced or metastatic MSS-CRC and has progressed was intolerant to at least 2 prior cancer therapy regimens administered for metastatic disease.
• Monotherapy Dose Optimization Cohorts:
• a) Participant has histologically confirmed diagnosis of locally advanced or metastatic MSS-CRC and has progressed or was intolerant to at least 2 prior cancer therapy regimens administered for metastatic disease.
• Combination Therapy Cohorts:
• a) For NSCLC Combination Therapy Cohort only:
• Participant has histologically confirmed or cytologically confirmed diagnosis of Stage IV NSCLC and has progressed on or after platinum-based chemotherapy and/or checkpoint inhibitors.
• Participant is eligible to receive docetaxel. b) For MSS CRC Combination Therapy Cohort only:
• Participant has histologically confirmed diagnosis of locally advanced or metastatic MSS-CRC.
• Participant must have progressed or was intolerant to at least 2 prior cancer therapy regimens administered for metastatic disease.
• Participant is eligible to receive TAS-102 and bevacizumab.
∙ Monotherapy and Combination Therapy Additional Backfill Participants:
• Participant has histologically confirmed diagnosis of Stage IV NSCLC and has progressed on or after receiving platinum based chemotherapy and/or checkpoint inhibitors in the first line of therapy.
• Participant has an Eastern Cooperative Oncology Group (ECOG) Status of 0 or 1.
• Monotherapy cohorts and combination dose escalation cohorts only:
• Participant's last dose of prior antineoplastic therapy, including any immunotherapy, was at least 21 days prior to the first dose of study intervention administration. A participant with solid tumors that have a NTRK gene fusion without a known acquired resistance mutation or EGFR or anaplastic lymphomas kinase (ALK) mutation-positive NSCLC is allowed to remain on EGFR tyrosine kinase inhibitor (TKI), ALK inhibitor therapy or NTRK inhibitor therapy until 4 days prior to the first dose of study intervention. Note: This is not applicable to participants with NSCLC in the combination dose expansion cohort.
• Participants who have received radiotherapy must have completed this therapy (including stereotactic radiosurgery) at least 2 weeks prior to the first dose of study intervention.
• Participant's adverse events (excluding alopecia) from prior therapy have resolved or improved to grade 1 at least 14 days prior to the first dose of study intervention. Note: Participants with type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy, or skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment are allowed.
• Participant has adequate organ function prior to start of study treatment (within 7 days prior to study intervention treatment initiation) as indicated by the following laboratory values. If a participant has received a recent blood transfusion, the laboratory tests must be obtained \>= 2 weeks after any blood transfusion: Absolute Neutrophil Count (ANC) \>= 1500/µL; Platelets \>= 100,000/µL; Hemoglobin \>= 9 g/dL (Criterion must be met without packed red blood cell transfusion within the 2 weeks prior. Participants can be on stable dose of erythropoietin (approximately ≥ 3 months); Creatinine clearance \>= 60 mL/min (calculated by Cockcroft-Gault equation); Total Bilirubin either (a) \<= 1.5 x ULN or (b) Direct bilirubin \<= ULN and total bilirubin \< 3 x ULN (for participants with Gilbert's syndrome); aspartate aminotransferase (AST) \[serum glutamic oxaloacetic transaminase (SGOT)\] and alanine aminotransferase (ALT) \[serum glutamic pyruvic transaminase (SGPT)\] \<= 2.5 x ULN without liver metastases (or \<= 5 x ULN if liver metastases are present); Thyroid stimulating hormone (TSH) within normal limits. Note: if TSH is not within normal limits at baseline, participant may still be eligible if T3 and/or FT4 are within the normal limits.
• Participant has activated partial thromboplastin time and international normalized ratio (INR) \<= 1.5 x ULN and is not receiving anticoagulation.
• Female participant is not pregnant and at least one of the following conditions apply:
‣ Not a woman of childbearing potential (WOCBP)
⁃ WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 45 days after final ASP1570 administration or at least 120 days after administration of pembrolizumab or standard therapies, whichever occurs later.
• Female participant must agree not to breastfeed starting at screening and throughout the study period and for at least 45 days after final ASP1570 administration or at least 120 days after administration of pembrolizumab or standard therapies, whichever occurs later.
• Female participant must not donate ova starting at first dose of study intervention and throughout the study period and for at least 45 days after final ASP1570 administration or at least 120 days after administration of pembrolizumab or standard therapies, whichever occurs later.
• Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for at least 45 days after final ASP1570 administration or at least 120 days after administration of pembrolizumab or standard therapies, whichever occurs later.
• Male participant must not donate sperm during the treatment period and for at least 45 days after final ASP1570 administration or at least 120 days after administration of pembrolizumab or standard therapies, whichever occurs later.
• Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for at least 45 days after final ASP1570 administration or at least 120 days after administration of pembrolizumab or standard therapies, whichever occurs later.
• Participant agrees not to participate in another interventional study while receiving study treatment in the present study.