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

Study Identifier:
1002-CL-0101
CT.gov Identifier:
NCT05719558
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
2024-512410-18-00
Study Contact Information:
(210) 593-5651 or [email protected]
Will Be Recruiting

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Study Summary

To learn if people with certain solid tumors have any medical problems or side effects after receiving different doses of ASP1002. To find a suitable dose of ASP1002 to use in future studies. To evaluate the safety and tolerability, maximum tolerated dose (MTD), and/or recommended phase 2 dose (RP2D) of ASP1002 in adult patients with LA or metastatic solid tumors that express CLDN4. ORR (confirmed CR or PR) per iRECIST will be evaluated in tumor-specific expansion cohorts.

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.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Bladder
Breast Cancers
Bowel (Colorectal)
Non-Small Cell Lung Cancer
Ovarian
Prostate
Renal
Solid Tumor
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase I
Sex
Female & Male
Age
18+ years
Study Drug
Drug: 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.
Study Status
Indicates the current recruitment status or the expanded access status
Will Be Recruiting

Requirements information
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:
  • Not a woman of childbearing potential (WOCBP)
  • 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:
  • Hepatitis A virus antibodies immunoglobulin (IgM)
  • 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.
  • 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.

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Study Locations

Location
Investigator
Status
Condition(s) Treated at Site
Location
START New York (Long Island)
Lake Success, NY, United States, 11042
Investigator
Geraldine O'Sullivan Coyne
Status
Will Be Recruiting
Condition(s) Treated at Site
Bladder
Breast Cancers
Bowel (Colorectal)
Non-Small Cell Lung Cancer
Ovarian
Prostate
Renal
Solid Tumor
Location
START Los Angeles
Los Angeles, CA, United States, 90025
Investigator
Navid Hafez
Status
Will Be Recruiting
Condition(s) Treated at Site
Bladder
Breast Cancers
Bowel (Colorectal)
Non-Small Cell Lung Cancer
Ovarian
Prostate
Renal
Solid Tumor