A study of ASP2074 in adults with solid tumors

JRCT ID: jRCT2031220554

Registered date:29/12/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Metastatic or locally advanced solid tumors
• Date of first enrollment: 28/02/2023
• Target sample size: 23
• Countries of recruitment: United States,Japan
• Study type: Interventional

Intervention(s)

This study will be in 2 parts.
1.ASP2074 Dose Escalation (Part 1)
Participants will be assigned to sequentially or in parallel escalating dose/regimen cohorts of ASP2074 in three parts (Part A, B and C). Part B and Part C will be opened sequentially based upon sponsor review of emerging data.
2.ASP2074 Dose Expansion (Part 2)
Colorectal Adenocarcinoma, Esophageal or Gastroesophageal junction (GEJ) Adenocarcinoma, Pancreatic Adenocarcinoma
Participants will receive ASP2074 with dose/regimen selected from dose escalation (Part 1).

ASP2074 will be given as an infusion on the first day of each treatment cycle. The participants in this study will have treatment cycles until: they have medical problems from the treatment; their cancer gets worse; they start other cancer treatment; they ask to stop treatment; or they do not come back for treatment.

Outcome(s)

Primary Outcome

-Dose Limiting Toxicities (DLTs)
-Adverse Events (AEs)
-Serious Adverse Events (SAEs)
-Clinical laboratory values
-Vital sign
-Routine 12-lead electrocardiogram

Secondary Outcome

-Objective Response Rate (ORR) per Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) and RECIST v1.1
-Duration of Response (DOR) per iRECIST and RECIST v1.1
-Disease Control Rate (DCR) per iRECIST and RECIST v1.1
-Serum CA19-9 levels in participants with pancreatic cancer
-Selected Pharmacokinetic (PK) parameters of ASP2074 in serum: Area under the concentration-time curve from time zero to 336 hours post dose (AUC[0-336h]), Maximum concentration (Cmax), Concentration immediately prior to dosing at multiple dosing (Ctrough), Time of maximum concentration (tmax)
-Changes in target antigen expression and CD8 infiltration/ activation in tumor

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Participant has locally-advanced (unresectable) or metastatic solid tumor malignancy (no limit to the number of prior treatment regimens) which is confirmed by available pathology records or current biopsy. For dose escalation, the participant must have colorectal, pancreatic, gastric cancer, esophageal or Gastroesophageal junction (GEJ) adenocarcinoma. For the tumor-specific expansion cohorts, the participant must have colorectal adenocarcinoma, esophageal or GEJ adenocarcinoma, or pancreatic adenocarcinoma.
2. 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.
3. Participant has progressed or failed to tolerate after receiving all standard approved therapies or is no longer eligible for standard therapy (no limit to the number of prior treatment regimens).
4. Participant has an Eastern Cooperative Oncology Group (ECOG) Status of 0 or 1.
5. Participants who have received radiotherapy must have completed this therapy (including stereotactic radiosurgery) at least 2 weeks prior to study intervention administration.
6. Participant's adverse events (excluding alopecia) from prior therapy have improved to grade 1 or baseline for the participant (e.g., grade 2 hypothyroidism) within 14 days prior to the first dose of study intervention.
7. Participant has predicted life expectancy >= 12 weeks.
8. Participant must meet all of the criteria based on laboratory tests. In case of multiple laboratory data within this period, the most recent data should be used. If a participant has received a recent blood transfusion, the laboratory tests must be obtained >= 2 weeks after any blood transfusion.
9. Female participant is not pregnant confirmed by serum pregnancy test and medical evaluation by interview and at least 1 of the following conditions apply:
o Not a woman of childbearing potential (WOCBP)
o WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 90 days after final study intervention administration.
10. Female participant must agree not to breastfeed starting at screening and throughout the study period and for 90 days after final study intervention administration.
11. Female participant must not donate ova starting at first dose of study intervention and throughout the study period and for 90 days after final study intervention administration.
12. Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 90 days after final study intervention administration.
13. Male participant must not donate sperm during the treatment period and for 90 days after final study intervention administration.
14. 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 90 days after final study intervention administration.
15. Participant agrees not to participate in another interventional study while receiving study treatment in the present study.

Exclude criteria

1. Participant has received other investigational agents or devices concurrently or within 21 days or 5 half-lives, whichever is shorter, prior to first dose of study intervention administration.
2. Participant has any condition which makes the participant unsuitable for study participation.
3. Participant has a known or suspected hypersensitivity to ASP2074 or any components of the formulation used.
4. Participants with squamous cell colorectal carcinoma; gastrointestinal stromal tumor and neuroendocrine carcinomas.
5. Participant weighs < 40 kg.
6. Participant requires or has received systemic steroid therapy or any other immunosuppressive therapy within 14 days prior to study intervention administration. Participants using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone or up to 10 mg per day prednisone), receiving a single dose of systemic corticosteroids, or receiving systemic corticosteroids as premedication for radiologic imaging contrast use is eligible.
7. Participant has symptomatic central nervous system (CNS) metastases or participant has evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans). Participants with previously treated CNS metastases are eligible, if they are clinically stable and have no evidence of CNS progression by imaging for at least 4 weeks prior to start of study treatment and are not requiring immunosuppressive doses of systemic steroids (> 30 mg per day of hydrocortisone or > 10 mg per day of prednisone or equivalent) for longer than 2 weeks.
8. Participant has an active autoimmune disease. 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.
9. Participant was discontinued from prior immunomodulatory therapy due to a grade >= 3 toxicity that was mechanistically related (e.g., immune related) to the agent.
10. Participant is known to have human immunodeficiency virus (HIV) infection. However, participants with HIV infection with CD4+ T-cell counts >= 350 cells/microL and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the past 6 months are eligible. NOTE: Screening for HIV infection should be conducted per local requirements.
11. Participant is known to have active hepatitis B (positive hepatitis B surface antigen (HBsAg)) or hepatitis C infection. NOTE: Screening for these infections should be conducted per local requirements.
o For participant who is negative for HBsAg, but hepatitis B core antibody (HBcAb) positive, a hepatitis B virus (HBV) DNA test will be performed and if positive the participant will be excluded.
o Participant with positive hepatitis C virus (HCV) serology, but negative HCV RNA test results are eligible.
o Participant treated for HCV with undetectable viral load results are eligible
12. Participant has received a live vaccine against infectious diseases within 28 days prior to initiation of study treatment.
13. Participant with a history of interstitial lung disease (ILD) or non-infectious pneumonitis, or currently has ILD/pneumonitis.
14. Participant has an infection requiring systemic therapy within 14 days prior to study drug treatment.
15. Participant has received a prior allogeneic bone marrow or solid organ transplant.
16. Participant is expected to require another form of antineoplastic therapy while on study treatment.
17. Participant with a history of the following significant cardiovascular disease will be excluded:
o Participant has inadequately controlled hypertension on antihypertensive medications.
o Participant has a history of myocardial infarction or unstable angina within 6 months prior to day 1.
o Participant has New York Heart Association Class II or greater Congestive heart failure (CHF).
o History of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to study treatment.
o Participant has significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to study treatment.
o Participant has cardiac arrhythmia, complete left bundle branch block, obligate use of a cardiac pacemaker, long time from the start of the Q wave to the end of the T wave (QT) syndrome or right bundle branch block with left anterior hemiblock (bifascicular block).
o Participant has a corrected QT interval (single ECG) using Fridericia's formula (QTcF) > 450 msec during screening. A single 12-lead ECG will be performed during screening.
18. Participant has had psychiatric illness/social situations that would limit compliance with study requirements.
19. Participant has a prior malignancy, other than the current malignancy for which the participant is seeking treatment, active (i.e., requiring treatment of intervention) within the previous 2 years except for locally curable malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
20. Participant has had major surgery within 28 days prior to the start of study treatment.

Related Information

• Primary Sponsor: Guseva Maria