A Study of ASP1002 in Adults for Treatment of Solid Tumors

A Phase 1 Study of ASP1002 in Participants With Metastatic or Locally Advanced Solid Tumors

ASP1002 is being studied in people with tumors that have spread to nearby tissue (locally advanced) that cannot be removed by surgery (unresectable) or tumors that have spread to other parts of the body (metastatic). Claudin 4 protein, or CLDN4, is a protein found on tumors in different parts of the body. ASP1002 is thought to work by attaching to the CLDN4 protein in the tumor. This switches on the body's immune system to attack the tumor.

Before ASP1002 can be used, researchers need to collect information about the safety of ASP1002 and how people with tumors tolerate it. In this study, ASP1002 will be given to humans for the first time. It will either be given by itself or together with other cancer treatments. These include standard chemotherapies (mFOLFOX6, FOLFIRI, TAS-102, pemetrexed, carboplatin, and docetaxel) and immunotherapies (bevacizumab, pembrolizumab, and ramucirumab). Immunotherapy is a treatment that works with the body's immune system to treat tumors.

This is an early development study. These studies are mostly about safety, but also to find the most suitable dose. Other aims are to learn if ASP1002 shows signs of slowing down tumor growth, to learn how the body processes ASP1002, and to check if there are changes in the CLDN4 protein or the immune system after treatment.

The main aims of the study are to check the safety of ASP1002 by itself and given with standard chemotherapies and immunotherapies in people with solid tumors and how well they tolerate the study treatments, and to find a suitable dose of ASP1002 by itself and in combination with standard chemotherapies and immunotherapies.

People in this study will be adults with tumors that have spread to nearby tissue (locally advanced) that cannot be removed by surgery (unresectable) or tumors that have spread to other parts of the body (metastatic). They will have been previously treated with available standard therapies, or they will have refused to receive those treatments.

The key reasons people cannot take part are if they have symptoms of cancer in the brain or nervous system, have recently had other cancers that required treatment, or have diseases that affect the immune system or the heart.

This study will be in 2 parts. In Part 1, different small groups of people will receive lower to higher doses of ASP1002 by itself and given with chemotherapies and immunotherapies. Any medical problems will be recorded at each dose. This is done to find suitable doses of ASP1002 to use in Part 2 of the study.

In Part 2, other different small groups of people will receive doses of ASP1002, the chemotherapies and immunotherapies that worked the best in Part 1.

In both parts of the study, ASP1002 will be given by itself and with standard chemotherapies and immunotherapies to people slowly through a tube into a vein. This is called an infusion. This will happen every 2 to 4 weeks, in treatment cycles. Treatment cycles may be 21 or 28 days long. People will continue to receive study treatment for up to 2 years or until their cancer gets worse, they can't tolerate the study treatment, they start other cancer treatments, or the doctor decides the person should stop receiving study treatment, or sadly, they pass away. They can also choose to stop taking the study treatment at any time without giving a reason.

During the study, people will visit the clinic several times for a health check. This includes standard safety checks and reporting any medical problems. Every 2 months, the study doctors will check if each person's cancer has stayed the same, shrunk or disappeared over time. This will be done by scans (CT or MRI scans). Tumor samples will be taken during the study, and people will have the option of giving a tumor sample after study treatment has finished.

People will have follow-up health checks for up to 1 year after their last dose of study treatment or until they start a different study treatment on a new study, whichever happens first.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Bevacizumab; Drug: Docetaxel; Drug: Carboplatin; Drug: Pemetrexed; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Irinotecan; Drug: Pembrolizumab; Drug: ASP1002; Drug: Fluorouracil; Drug: Trifluridine-Tipiracil; Drug: Ramucirumab

• Study Type: Interventional
• Enrollment (Estimated): 798
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Astellas Pharma Global Development, Inc.; Phone Number: 800-888-7704; Email: Astellas.registration@astellas.com

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University Cancer Center
    • Plainville, Connecticut, United States, 06062
      • Recruiting
      • Hartford HealthCare Cancer Institute at The Hospital of Central Connecticut
  • Florida
    • Gainesville, Florida, United States, 32610
      • Recruiting
      • University of Florida
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Hospital
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Recruiting
      • HealthPartners Cancer Research Center
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals of Cleveland
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Completed
      • Prisma Health-Upstate Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Completed
      • SCRI Oncology Partners
  • Texas
    • Dallas, Texas, United States, 75251
      • Recruiting
      • Mary Crowley Cancer Research Center
    • Dallas, Texas, United States, 75235
      • Completed
      • University of Texas Southwestern
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Oncology Virginia
  • Washington
    • Edmonds, Washington, United States, 21632
      • Recruiting
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

For Monotherapy:

• Participant has locally-advanced (unresectable or metastatic solid tumor) confirmed by available pathology records or current biopsy.

  a. For monotherapy dose escalation, participant must have one of the following malignancies:NSCLC-adenocarcinoma, squamous cell carcinoma and adenosquamous are included; large cell carcinoma and sarcomatoid carcinoma are excluded, UC, CRC, prostate adenocarcinoma, epithelial ovarian cancer (including fallopian tube cancer) and triple-negative breast cancer (TNBC).

• TNBC defined as unequivocal TNBC histology (ER 1 negative/progesterone receptor-negative/HER2-negative). This is defined by < 1% expression of ER and progesterone receptor by IHC and that are, for HER2, either 0 to 1+ by IHC, or IHC 2+ and FISH negative (not amplified) as per current ASCO/CAP guidelines [Hammond et al, 2010].

  b. For tumor-specific monotherapy dose expansion, participant must have one of the following malignancies mCRC, mAPMR-PCa and tumor type for which a confirmed response was observed during dose escalation.

• Monotherapy expansion mCRC/mAPMR-PCa cohort: Participants with MSS/MSI-L mCRC/mAPMR-PCa, are eligible.
• Monotherapy expansion select CLDN4-expressing tumors cohort: Participants with metastatic solid tumors known to highly express CLDN4 are eligible.
• Participant has progressed, is intolerant, has refused, or there are no approved therapies that impart significant clinical benefit (no limit to the number of prior treatment regimens).

• Female participant is not pregnant, confirmed by pregnancy test (and medical evaluation by interview and at least 1 of the following conditions apply:

  1. Not a woman of childbearing potential (WOCBP)
  2. WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 90 days after final ASP1002 study intervention administration.
• Participant has progressed, is intolerant, has refused, or there are no standard approved therapies that impart significant clinical benefit (no limit to the number of prior treatment regimens).
• Participant has accessible archival tumor tissue (< 6 months old at the date of consent) from either the primary tumor or a metastatic site, with source and availability confirmed prior to Cycle 1 Day 1 (C1D1); participants without available tissue should undergo a mandatory biopsy. Participant should undergo a tumor biopsy during the treatment period as indicated in the schedule of assessments. Note: Tumor tissue collection (at screening/baseline and on-treatment) is optional for participants enrolled initially in dose levels 1 to 3 in dose escalation; however, protocol de-escalation and expansion of dose levels similar to dose levels 1 to 3 may require collection and processing of screening/baseline and on-treatment tumor samples.
• Participant has at least 1 measurable lesion per RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Eastern Cooperative Oncology Group (ECOG) Status of 0 or 1 within 7 days before the first dose of study drug.
• Participants who received radiotherapy must have completed it at least 2 weeks prior to study intervention administration.
• Participant has predicted life expectancy >/= 12 weeks.
• Participant has adequate organ function prior to start of study intervention. In case of recent blood transfusion, laboratory tests must be obtained >/=2 weeks post transfusion.
• Female participants must not breastfeed from screening through 90 days post-final dose and must not donate ova from first dose through 90 days post-final dose.
• Male participants with WOCBP partners must use contraception during treatment and for 90 days post-final dose.
• Male participants must not donate sperm during treatment and for 90 days post-final dose, and those with pregnant partners must remain abstinent or use condoms for the duration of the pregnancy and 90 days post-final dose.
• Participant agrees not to participate in another interventional study while receiving any study intervention in the present study.

For Combination-therapy:

• Participant has accessible archival tumor tissue (< 6 months old at the date of consent) from either the primary tumor or a metastatic site, for which source and availability have been confirmed prior to C1D1. Participant should undergo a tumor biopsy during the treatment period as indicated in the schedules of assessments.
• Participant has at least 1 measurable lesion per RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• ECOG Status of 0 or 1 within 7 days before the first dose of study drug.
• Participant has adequate organ function prior to start of study intervention as indicated by laboratory values. If a participant has received a recent blood transfusion, the laboratory tests must be obtained ≥ 2 weeks after any blood transfusion.
• Female participant is not pregnant as confirmed by pregnancy test, not breastfeeding and must not donate ova starting at first administration of study intervention and for at least 9 months after final study intervention administration
• Not a WOCBP
• WOCBP must adhere to required contraception from informed consent through 9 months post-final study intervention.
• Male participant must not donate sperm during the treatment period and for at least 6 months after final study intervention administration.

Combination-specific Inclusion Criteria for MSS-mCRC (2L) ASP1002 + bevacizumab + mFOLFOX6

• Participant has MSS-mCRC which is confirmed by available pathology records or current biopsy. Participant is AGA-negative and HER2-negative.
• Participant has progressed or is intolerant to 1L irinotecan-based therapy for their metastatic disease. Participant is eligible to receive mFOLFOX6 and bevacizumab.
• WOCBP must adhere to required contraception from informed consent through 9 months post-final study intervention.
• Female participants must not breastfeed from screening through 6 months post-final dose and must not donate ova from first dose through 9 months post-final dose.
• Male participants with WOCBP partners must use contraception during treatment and for 6 months post-final dose.
• Male participants must not donate sperm during treatment and for 6 months post-final dose, and those with pregnant partners must remain abstinent or use condoms for the duration of the pregnancy and 6 months post-final dose.

Combination-specific Inclusion Criteria for MSS-mCRC (2L) ASP1002 + bevacizumab + FOLFIRI

• Participant has MSS-mCRC confirmed by pathology records/current biopsy. Participant is AGA-negative and HER2-negative.
• Participant has progressed or is intolerant to 1L oxaliplatin-based therapy for their metastatic disease. Participants who have received oxaliplatin as adjuvant therapy and had disease relapse < 12 months from completion of adjuvant therapy are eligible. Participant is eligible to receive FOLFIRI and bevacizumab.
• WOCBP must adhere to required contraception from informed consent through 6 months post-final study intervention.
• Female participants must not breastfeed from screening through 6 months post-final dose and must not donate ova from first dose through 6 months post-final dose.
• Male participants with WOCBP partners must use contraception during treatment and for 6 months post-final dose.
• Male participants must not donate sperm during treatment and for 6 months post-final dose, and those with pregnant partners must remain abstinent or use condoms for the duration of the pregnancy and 6 months post-final dose.

Combination-specific Inclusion Criteria for MSS-mCRC (3L) AGA-negative, HER2-negative ASP1002 + bevacizumab + TAS-102

• Participant has MSS-mCRC and has progressed radiographically on or was intolerant to previous therapy with a fluoropyrimidine, irinotecan and oxaliplatin, with/without anti-VEGF monoclonal antibody; with/without an anti-EGFR monoclonal antibody (if RAS wild-type); and a BRAF inhibitor (if known BRAFV600E [i.e., Val600Glu] mutation) for their metastatic disease.
• WOCBP must adhere to required contraception from informed consent through 6 months post-final study intervention.
• Female participants must not breastfeed from screening through 6 months post-final dose and must not donate ova from first dose through 6 months post-final dose.
• Male participants with WOCBP partners must use contraception during treatment and for 6 months post-final dose.
• Male participants must not donate sperm during treatment and for 6 months post-final dose, and those with pregnant partners must remain abstinent or use condoms for the duration of the pregnancy and 6 months post-final dose.

Combination-specific Inclusion Criteria for MSS-mCRC (4L) ASP1002 + bevacizumab

• Participant has MSS-mCRC confirmed by pathology records/current biopsy.
• Participant has progressed or is intolerant to 5-FU, oxaliplatin and irinotecan containing regimens as well as only one of the following: TAS-102 ± bevacizumab, fruquintinib or regorafenib.
• WOCBP must adhere to required contraception from informed consent through 6 months post-final study intervention.
• Female participants must not breastfeed from screening through 6 months post-final dose and must not donate ova from first dose through 6 months post-final dose.
• Male participants with WOCBP partners must use contraception during treatment and for 6 months post-final dose.
• Male participants must not donate sperm during treatment and for 6 months post-final dose, and those with pregnant partners must remain abstinent or use condoms for the duration of the pregnancy and 6 months post-final dose.

Combination-specific Inclusion Criteria for NSCLC (1L) ASP1002 + pembrolizumab + pemetrexed + carboplatin

• Participant has PD-L1 low or negative (TPS < 50 %) TPS = 1% to 49% or negative (TPS < 1%) and AGA-negative Stage IV adenocarcinoma (mixed histology is not allowed).
• Participant has metastatic adenocarcinoma of the lung, confirmed by pathology records/current biopsy. Participant has not received prior systemic treatment for their advanced/metastatic NSCLC. Participant who remains disease free for 12 months following the completion of neoadjuvant/adjuvant treatment is eligible. Participant is eligible to receive pembrolizumab + pemetrexed + carboplatin.
• WOCBP must adhere to required contraception from informed consent through 6 months post-final study intervention.
• Female participants must not breastfeed from screening through 6 months post-final dose and must not donate ova from first dose through 6 months post-final dose.
• Male participants with WOCBP partners must use contraception during treatment and for 6 months post-final dose.
• Male participants must not donate sperm during treatment and for 6 months post-final dose, and those with pregnant partners must remain abstinent or use condoms for the duration of the pregnancy and 6 months post-final dose.

Combination-specific Inclusion Criteria for NSCLC (2L/3L) ASP1002 + ramucirumab + docetaxel

• Participant has Stage IV NSCLC without AGA and has progressed after a platinum-based chemotherapy and a checkpoint inhibitor either concomitantly or in sequence (for participants who received a checkpoint inhibitor as monotherapy in the first line for NSCLC with TPS ≥ 50%).
• Participant is eligible to receive docetaxel and ramucirumab.
• WOCBP must adhere to required contraception from informed consent through 3 months post-final study intervention.
• Female participants must not breastfeed from screening through 3 months post-final dose and must not donate ova from first dose through 3 months post-final dose.
• Male participants with WOCBP partners must use contraception during treatment and for 4 months post-final dose.
• Male participants must not donate sperm during treatment and for 4 months post-final dose, and those with pregnant partners must remain abstinent or use condoms for the duration of the pregnancy and 4 months post-final dose.

Combination-specific Inclusion Criteria for Select CLDN4-expressing Tumors ASP1002 + pembrolizumab

• Participant has histologically confirmed metastatic solid tumor known to highly express CLDN4 based on published literature, as determined by the sponsor. Individual tumor testing for CLDN4 expression is not required.
• Participant has progressed, is intolerant, has refused, or there are no standard approved therapies that impart significant clinical benefit(s).Participant is eligible to receive pembrolizumab.
• WOCBP must adhere to required contraception from informed consent through 6 months post-final study intervention.
• Female participants must not breastfeed from screening through 120 days post-final dose and must not donate ova from first dose through 120 days post-final dose.
• Male participants with WOCBP partners must use contraception during treatment and for 120 days post-final dose.
• Male participants must not donate sperm during treatment and for 120 days post-final dose, and those with pregnant partners must remain abstinent or use condoms for the duration of the pregnancy and 120 days post-final dose.

Exclusion Criteria

• Participant weighs < 40 kg.
• Ongoing toxicity that has not resolved to ≤ grade 1 per CTCAE version 5.0 and is considered clinically significant and in the opinion of the investigator, attributable to prior antineoplastic therapy.
• Symptomatic CNS metastases or evidence of uncontrolled CNS disease even if asymptomatic (e.g. progression on scans). Participants with previously treated CNS metastases are eligible, if they are clinically stable/have no evidence of CNS progression by imaging for at least 4 weeks prior to start of study intervention and are not requiring immunosuppressive doses of systemic steroids (equivalent to > 10 mg per day of prednisone) for longer than 2 weeks.
• Active autoimmune disease, a history of inflammatory bowel disease (IBD)or other immune-related GI disorders (e.g., ulcerative colitis, Crohn's disease). Participant 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.
• Myocardial infarction or unstable angina within 6 months prior to the start of study intervention or currently has an uncontrolled illness including, but not limited to, symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, complete left bundle branch block, obligate use of a cardiac pacemaker, long QT syndrome, right bundle branch block with left anterior hemiblock (bifascicular block) or severe hypertension not controlled with medical management.
• Corrected QT interval (QTcF) interval (single electrocardiogram (ECG)) > 470 ms within 7 days prior to the first study intervention administration on day 1.
• Participant has left ventricular ejection fraction (LVEF) < 45% noted in screening echocardiogram (ECHO). Any clinically significant findings from this ECHO should be discussed with the medical monitor.
• Participant with human immunodeficiency virus (HIV) infection. However, participants with HIV infection with CD4+ T cell counts >/=350 cells/μL and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections within the past 6 months or controlled disease on stable HAART without evidence of uncontrolled infection or clinically-relevant drug interactions with ASP1002 are eligible.

• Any of the following per screening serology test:

  1. Hepatitis A virus antibodies immunoglobulin (IgM)
  2. Positive HBsAg or detectable hepatitis B DNA. Participant with negative HBsAg, positive anti-HBc, must have HBV DNA testing performed.Participant is eligible if hepatitis B DNA is undetectable.
  3. hepatitis C virus (HCV) antibodies unless HCV Ribonucleic acid (RNA) is undetectable d HCV antibodies, and antigens (UNIQUE to Japan), unless HCV RNA is undetectable.
• History of drug or radiation induced pneumonitis, interstitial lung disease (ILD), currently has pneumonitis, or prior history of ILD/non-infectious pneumonitis requiring high-dose glucocorticoids.
• Unique to Japan: History of interstitial pneumonia.
• Uncontrolled intercurrent illness including, ongoing or active infection, symptomatic congestive heart failure, substance abuse or psychiatric illness/social situations that would limit compliance with study visits or requirements or a condition that could invalidate communication with the investigator.
• Participant has received a prior allogeneic bone marrow or solid organ transplant.
• Participant has had major surgical procedure and has not completely recovered within 28 days prior to the start of study intervention.
• Recent positive antigen test for Coronavirus Disease 2019 (COVID-19) within 10 days prior to study intervention administration.
• Participant has received any investigational therapy or antineoplastic therapy (anti-tumor traditional Chinese medicine within 14 days) prior to the start of study intervention administration, or other immunotherapy within 21 days or 5 half-lives, whichever is longer, prior to the first dose of study intervention.
• Participant requires or has received systemic steroid therapy or any other immunosuppressive therapy within 14 days prior to ASP1002 administration. Participants using a physiologic replacement dose of corticosteroids equivalent to 10 mg per day of prednisone or less are allowed, as is receiving a single dose of systemic corticosteroids, or receiving systemic corticosteroids as premedication for radiologic imaging contrast is eligible.
• Participant was discontinued from prior immunomodulatory therapy due to a grade >/=3 toxicity that was mechanistically related (e.g., immune-related) to the agent and deemed life-threatening.
• Participant is expected to require another form of antineoplastic therapy while on study intervention.
• Malignancy requiring active therapy.
• Participants who have received prior anti-CD137 therapy.
• Participant has received a live or attenuated vaccine against infectious diseases within 28 days prior to initiation of study intervention.
• Any condition makes the participant unsuitable for study participation.
• Known or suspected hypersensitivity to ASP1002 bevacizumab, mFOLFOX6 or any components of the formulation used.
• leptomeningeal disease.
• Increased risk of bleeding or hepatic impairment-associated coagulopathy, defined as aPTT or INR > 1.5 × ULN (in the absence of therapeutic anticoagulation), or clinically significant bleeding within a clinically relevant timeframe as per the investigator's judgement.
• Prior malignancy, other than the current malignancy for which the participant is seeking treatment, active (i.e., requiring treatment or 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.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of participant to participate, in the opinion of the treating investigator.

Unique to China: participant has a positive HIV antibody test result.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

18

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy Dose Escalation (Part 1); Participants will receive sequentially escalating doses of ASP1002. Each dose level will open sequentially based upon sponsor review of emerging data.	Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.
Experimental: Monotherapy Dose Expansion (Part 2) in microsatellite stable metastatic colorectal cancer(MSS-mCRC); Participants will receive ASP1002 with dose/regimen selected from dose escalation (Part 1).	Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.
Experimental: Monotherapy Dose Expansion (Part 2) in microsatellite stable prostate cancer(MSS-Pca); Participants will receive ASP1002 with dose/regimen selected from dose escalation (Part 1).	Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.
Experimental: Monotherapy Dose Expansion (Part 2) in tumors highly expressing CLDN4 protein; Participants with tumors highly expressing CLDN4 protein will receive ASP1002 with dose/regimen selected from dose escalation (Part 1).	Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.
Experimental: Combination Therapy Dose Escalation Part 1: ASP1002 + bevacizumab + FOLFIRI- 2L MSS-mCRC; Participants with MSS-mCRC will receive sequentially escalating doses of ASP1002 in combination with bevacizumab and FOLFIRI as a second line therapy.	Drug: Bevacizumab; IV infusion; Drug: Leucovorin; IV infusion; Drug: Irinotecan; IV infusion; Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.; Drug: Fluorouracil; IV infusion
Experimental: Combination Therapy Dose Escalation Part 1: ASP1002 + bevacizumab + mFOLFOX6- 2L MSS-mCRC; Participants with MSS-mCRC will receive sequentially escalating doses of ASP1002 in combination with bevacizumab and mFOLFOX6 as a second line therapy.	Drug: Bevacizumab; IV infusion; Drug: Oxaliplatin; IV infusion; Drug: Leucovorin; IV infusion; Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.; Drug: Fluorouracil; IV infusion
Experimental: Combination Therapy Dose Escalation Part 1: ASP1002 + bevacizumab + TAS-102- 3L MSS-mCRC; Participants with MSS-mCRC will receive sequentially escalating doses of ASP1002 in combination with bevacizumab and TAS-102 as a third line therapy.	Drug: Bevacizumab; IV infusion; Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.; Drug: Trifluridine-Tipiracil; Film-coated tablet
Experimental: Combination Therapy Dose Escalation Part 1: ASP1002 + bevacizumab- 4L MSS-mCRC; Participants with MSS-mCRC will receive sequentially escalating doses of ASP1002 in combination with bevacizumab as fourth line therapy.	Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.
Experimental: Combination Therapy Dose Escalation Part 1: ASP1002+pembrolizumab+pemetrexed+carboplatin-1L NSCLC; Participants with non-small cell lung cancer (NSCLC) will receive sequentially escalating doses of ASP1002 in combination with pembrolizumab, pemetrexed and carboplatin as a first line therapy.	Drug: Carboplatin; IV infusion; Drug: Pemetrexed; IV infusion; Drug: Pembrolizumab; IV infusion; Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.
Experimental: Combination Therapy Dose Escalation Part 1: ASP1002 + docetaxel + ramucirumab- 2L/3L NSCLC; Participants with NSCLC will receive sequentially escalating doses of ASP1002 in combination with docetaxel and ramucirumab as second/ third line therapy.	Drug: Docetaxel; IV infusion; Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.; Drug: Ramucirumab; IV infusion
Experimental: Combination Therapy Dose Escalation Part 1: ASP1002 + pembrolizumab- CLDN4-expressing solid tumors; Participants with CLDN4-expressing solid tumors will receive sequentially escalating doses of ASP1002 in combination with pembrolizumab.	Drug: Pembrolizumab; IV infusion; Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.
Experimental: Combination Therapy Dose Expansion Part 2: ASP1002 + bevacizumab + mFOLFOX6- 2L MSS-mCRC; Participants with MSS-mCRC will receive ASP1002 in combination with bevacizumab and mFOLFOX6 with dose/regimen selected from dose escalation (Part 1) as a second line therapy.	Drug: Bevacizumab; IV infusion; Drug: Oxaliplatin; IV infusion; Drug: Leucovorin; IV infusion; Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.; Drug: Fluorouracil; IV infusion
Experimental: Combination Therapy Dose Expansion Part 2: ASP1002 + bevacizumab + FOLFIRI- 2L MSS-mCRC; Participants with MSS-mCRC will receive ASP1002 in combination with bevacizumab and FOLFIRI with dose/regimen selected from dose escalation (Part 1) as a second line therapy.	Drug: Bevacizumab; IV infusion; Drug: Leucovorin; IV infusion; Drug: Irinotecan; IV infusion; Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.; Drug: Fluorouracil; IV infusion
Experimental: Combination Therapy Dose Expansion Part 2: ASP1002 + bevacizumab + TAS-102- 3L MSS-mCRC; Participants with MSS-mCRC will receive ASP1002 in combination with bevacizumab and TAS-102 with dose/regimen selected from dose escalation (Part 1) as a third line therapy.	Drug: Bevacizumab; IV infusion; Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.; Drug: Trifluridine-Tipiracil; Film-coated tablet
Experimental: Combination Therapy Dose Expansion Part 2: ASP1002 + bevacizumab- 4L MSS-mCRC; Participants with MSS-mCRC will receive ASP1002 in combination with bevacizumab with dose/regimen selected from dose escalation (Part 1) as fourth line therapy.	Drug: Bevacizumab; IV infusion; Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.
Experimental: Combination Therapy Dose Expansion Part 2: ASP1002+pembrolizumab+pemetrexed +carboplatin-1L NSCLC; Participants with non-small cell lung cancer (NSCLC) will receive ASP1002 in combination with pembrolizumab, pemetrexed and carboplatin with dose/regimen selected from dose escalation (Part 1) as a first line therapy.	Drug: Carboplatin; IV infusion; Drug: Pemetrexed; IV infusion; Drug: Pembrolizumab; IV infusion; Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.
Experimental: Combination Therapy Dose Expansion Part 2: ASP1002+ ramucirumab + docetaxel- 2L/3L NSCLC; Participants with NSCLC will receive ASP1002 in combination with Ramucirumab and Docetaxel with dose/regimen selected from dose escalation (Part 1) as a second/third line therapy.	Drug: Docetaxel; IV infusion; Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.; Drug: Ramucirumab; IV infusion
Experimental: Combination Therapy Dose Expansion Part 2: ASP1002 + pembrolizumab- CLDN4-expressing solid tumors; Participants with CLDN4-expressing solid tumors will receive ASP1002 in combination with pembrolizumab with dose/regimen selected from dose escalation (Part 1).	Drug: Pembrolizumab; IV infusion; Drug: ASP1002; Intravenous (IV) infusion. Dose interruptions, reductions, and treatment discontinuations will be implemented according to protocol-defined toxicity management criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Events (AEs)	Adverse events (AEs) will be coded using MedDRA. An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to 25 months
Number of participants with Serious Adverse Events (SAEs)	A Serious Adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or other medically important event.	Up to 27 months
Number of participants with laboratory value abnormalities and/or adverse events (AEs)	Number of participants with potentially clinically significant laboratory values.	Up to 27 months
Number of participants with vital sign abnormalities and/or adverse events (AEs)	Number of participants with potentially clinically significant vital sign values.	Up to 27 months
Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)	Number of participants with potentially clinically significant ECG values.	Up to 27 months
Number of participants with physical exam abnormalities and/or Adverse Events (AEs)	Number of participants with potentially clinically significant physical exam values.	Up to 24 months
Number of participants at each grade of Eastern Cooperative Oncology Group (ECOG) performance status scores	The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 4 (completely disabled). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.	Up to 27 months
Incidence of Dose Limiting Toxicities (DLTs) for ASP1002	A DLT is defined as any of the following AEs that the investigator (or sponsor) cannot clearly attribute to a cause other than study intervention.	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK) of ASP1002 in serum: Cmax	Maximum concentration (Cmax) will be recorded from the PK serum samples collected.	Up to 12 months
Pharmacokinetics (PK) of ASP1002 in serum: Ctrough	Concentration immediately prior to dosing at multiple dosing (Ctrough) will be recorded from the PK serum samples collected.	Up to 12 months
Pharmacokinetics (PK) of ASP1002 in serum: tmax	Time of maximum concentration (tmax) will be recorded from the PK serum samples collected.	Up to 12 months
Objective Response Rate (ORR) per Immune Response Evaluation Criteria in Solid Tumors (iRECIST)	ORR is defined as the proportion of participants whose best overall response is a Complete Response (CR) or Partial Response (PR).	Up to 28 months
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	ORR is defined as the proportion of participants whose best overall response is a Complete Response (CR) or Partial Response (PR).	Up to 28 months
Duration of Response (DOR) per iRECIST	DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented disease progression (PD) or death due to any cause, whichever occurs first.	Up to 28 months
Duration of Response (DOR) per RECIST v1.1	DOR is defined as the time from the date of first documented response (CR or PR) to the date of first documented disease progression (PD) or death due to any cause, whichever occurs first.	Up to 28 months
Disease Control Rate (DCR) per iRECIST	DCR is defined as the proportion of participants whose best overall response is CR, PR or stable disease (SD).	Up to 28 months
Disease Control Rate (DCR) per RECIST v1.1	DCR is defined as the proportion of participants whose best overall response is CR, PR or stable disease (SD).	Up to 28 months
Incidence rate of Claudin-4 (CLDN4) by immunohistochemistry (IHC)	Characterization of CLDN4 expression in tumor biopsies at baseline and up to six weeks will be performed.	Baseline and up to 6 weeks
Changes in expression levels of Claudin-4 (CLDN4) by immunohistochemistry (IHC)	Comparison of CLDN4 expression at baseline versus on-treatment tumor biopsies will be performed.	Baseline and up to 6 weeks
Pharmacokinetics (PK) of ASP1002 in serum: Area under the concentration-time curve from time zero to time of the last measurable concentration (AUC0-tlast)	AUC0-tlast will be recorded from the PK serum samples collected.	Up to 12 months
Radiographic disease progression	Radiographic disease progression will be assessed by CT/MRI per RECIST v1.1 and iRECIST, and by bone scan according to PCWG4 criteria (applicable for evaluation of bone lesions in participants with mAPMR-PCa).	Baseline and up to 28 months
Prostate-Specific Antigen (PSA) Response Rate (PSA50)	PSA response will be assessed per Prostate Cancer Working Group 3 (PCWG3) criteria for metastatic androgen pathway modulation resistant (mAMPR) prostate cancer participants. Percentage of participants with a ≥50% decrease from baseline in PSA levels, confirmed by a subsequent assessment at least 3 weeks later.	Baseline and up to 28 months
Time to PSA Progression	PSA testing will be performed for mAMPR prostate cancer participants. Time from baseline (or PSA nadir) to first documented increase in PSA, confirmed by a second rising value at least 3 weeks later. A minimum rise of 0.2 ng/mL is required. The date of progression is defined as the date of the first increase.	Baseline and up to 28 months

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Investigators: Study Director: Medical Director, Astellas Pharma Global Development, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2023
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): May 31, 2030

Study Registration Dates

• First Submitted: January 31, 2023
• First Submitted That Met QC Criteria: January 31, 2023
• First Posted (Actual): February 9, 2023

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 22, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; cancer;; Solid Tumor;; Malignancy;; Metastasis;; ASP1002;; microsatellite stable metastatic colorectal cancer (MSS-mCRC)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms; Neoplasm Metastasis; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Camptothecin; Alkaloids; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Docetaxel; Oxaliplatin; Bevacizumab; Irinotecan; Pemetrexed; Ramucirumab; Fluorouracil; Carboplatin; Leucovorin; trifluridine tipiracil drug combination; pembrolizumab
• Other Study ID Numbers: 1002-CL-0101; 2024-512410-18-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No