ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of ASP1948, Targeting an Immune Modulatory Receptor, in Subjects With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03565445
Recruitment Status : Recruiting
First Posted : June 21, 2018
Last Update Posted : October 31, 2018
Sponsor:
Collaborator:
Potenza Therapeutics
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Brief Summary:
The purpose of this study is to evaluate the tolerability and safety profile of ASP1948 in participants with locally advanced (unresectable) or metastatic solid tumors; characterize the pharmacokinetic profile of ASP1948 and determine the recommended Phase 2 dose (RP2D) of ASP1948. This study will also evaluate the antitumor effect of ASP1948.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: ASP1948 Phase 1

Detailed Description:

This is a dose-escalation and expansion study of ASP1948. The study consists of 3 periods: screening, treatment and follow up, followed by an optional Re-treatment period for participants that qualify.

The escalation cohorts will evaluate escalating dose levels of ASP1948 in participants with locally advanced (unresectable) or metastatic solid tumor malignancies.

After discontinuation of study drug, all participants will complete an end-of-treatment visit, along with 30-day and 90-day safety follow-up visits.

For dose expansion, the tumor-specific cohorts will include participants with squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), metastatic castration-resistant prostate cancer (mCRPC), ovarian cancer, melanoma and breast cancer, as well as any tumor types that respond to study drug treatment during dose escalation.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 254 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of ASP1948, Targeting an Immune Modulatory Receptor, in Subjects With Advanced Solid Tumors
Actual Study Start Date : July 2, 2018
Estimated Primary Completion Date : July 2022
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ASP1948 Dose Escalation
The monotherapy escalation cohort will evaluate escalating dose levels of ASP1948. Each dose level will enroll approximately 3 or 4 participants. Dose escalation to the next level will be made based on the Bayesian Continual Reassessment Method (CRM).
Drug: ASP1948
Intravenously (IV)

Experimental: ASP1948 Dose Expansion
If a confirmed response (iRECIST partial response (iPR) or iRECIST confirmed response (iCR)) per iRECIST occurs in a monotherapy escalation cohort, a tumor specific expansion cohort may be opened in that tumor type, at the dose level in which the confirmed response was observed and at all subsequent dose levels once each dose level has been cleared. Up to 5 expansion cohorts may be opened.
Drug: ASP1948
Intravenously (IV)

Experimental: ASP1948 Optional Retreatment Period
Participants may reinitiate study drug treatment after confirmation that they meet all the re-treatment eligibility criteria.
Drug: ASP1948
Intravenously (IV)




Primary Outcome Measures :
  1. Safety and tolerability assessed by dose limiting toxicities (DLTs) [ Time Frame: Up to 28 days ]
    A DLT is defined as any of the prespecified Adverse Events (AEs) (graded using National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE] version 4.03) that the investigator (or sponsor) cannot clearly attribute to a cause other than study drug.

  2. Safety and tolerability assessed by Adverse Events (AEs) [ Time Frame: Up to a maximum of 52 weeks ]
    Initial and retreatment. An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. AEs will be coded using medical dictionary for regulatory activities (MedDRA) and graded using NCI-CTCAE version 4.03.

  3. Safety and tolerability assessed by immune-related Adverse Events (irAEs) [ Time Frame: Up to a maximum of 52 weeks ]
    Initial and retreatment. Most frequent immune-related AEs include rash, oral mucositis, dry mouth, colitis/diarrhea, hepatitis, pneumonitis, and endocrinopathies.

  4. Safety and tolerability assessed by infusion-related reaction (IRRs) [ Time Frame: Up to a maximum of 52 weeks ]
    Initial and retreatment. IRRs are considered AEs of special interest. In the event a participant is diagnosed with an IRR, then it should be reported as an AE.

  5. Safety and tolerability assessed by Serious Adverse Events (SAEs) [ Time Frame: Up to a maximum of 60 weeks ]
    Initial and retreatment. An AE is considered "serious" if, it results in any of the following outcomes: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures as allowed per study) or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE). Hospitalization for treatment/observation/examination caused by AE is to be considered as serious; and other medically important events.

  6. Number of participants with laboratory value abnormalities and/or adverse events [ Time Frame: Up to a maximum of 52 weeks ]
    Initial and retreatment. Number of participants with potentially clinically significant laboratory values.

  7. Safety assessed by 12- lead electrocardiogram (ECG) [ Time Frame: Up to a maximum of 48 weeks for each treatment period ]
    Initial and retreatment. ECGs should be obtained after the participant has rested quietly and is awake in a fully supine position (or semi-recumbent, if supine is not tolerated) for 10 minutes before the first ECG from a triplicate or single ECG. For ECGs done in triplicate, there should be at least 2 minutes between each ECG. Any abnormal ECGs including those that worsen from baseline, that is considered to be clinically significant and not related to underlying disease, is to be reported as an (S)AE.

  8. Number of participants with vital signs abnormalities and/or adverse events [ Time Frame: Up to a maximum of 60 weeks ]
    Initial and retreatment. Number of participants with potentially clinically significant vital sign values.

  9. Number of participants with Physical Exam abnormalities and/or adverse events [ Time Frame: Up to a maximum of 48 weeks for each treatment period ]
    Initial and retreatment. Number of participants with potentially clinically significant physical exam values.

  10. Safety assessed by Eastern Cooperative Oncology Group Performance Status (ECOG PS) [ Time Frame: Up to a maximum of 52 weeks ]

    Initial and retreatment. 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.


  11. Pharmacokinetics (PK) of ASP1948 in serum: AUClast [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Area under the concentration time curve from the time of dosing to the last measurable concentration (AUClast) will be derived from the pharmacokinetic (PK) serum samples collected.

  12. Pharmacokinetics (PK) of ASP1948 in serum: AUCinf [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Area under the concentration time curve from the time of dosing extrapolated to time infinity (AUCinf) will be derived from the pharmacokinetic (PK) serum samples collected.

  13. Pharmacokinetics (PK) of ASP1948 in serum: AUCinf %extrap [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Percentage of AUCinf due to extrapolation from time of the last measurable concentration to time infinity (AUCinf %extrap) will be derived from the pharmacokinetic (PK) serum samples collected.

  14. Pharmacokinetics (PK) of ASP1948 in serum: AUCtau [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Area under the concentration-time curve from the time of dosing to the start of next dosing interval (AUCtau) will be derived from the pharmacokinetic (PK) serum samples collected.

  15. Pharmacokinetics (PK) of ASP1948 in serum: Cmax [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Maximum concentration (Cmax) will be derived from the pharmacokinetic (PK) serum samples collected.

  16. Pharmacokinetics (PK) of ASP1948 in serum: Ctrough [ Time Frame: Up to a maximum of 48 weeks for each treatment period ]
    Initial and retreatment. Concentration immediately prior to dosing at multiple dosing (Ctrough) will be derived from the pharmacokinetic (PK) serum samples collected.

  17. Pharmacokinetics (PK) of ASP1948 in serum: tmax [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Time of the maximum concentration (tmax) will be derived from the pharmacokinetic (PK) serum samples collected.

  18. Pharmacokinetics (PK) of ASP1948 in serum: t1/2 [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Terminal elimination half-life (t1/2) will be derived from the pharmacokinetic (PK) serum samples collected.

  19. Pharmacokinetics (PK) of ASP1948 in serum: tlast [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Time of last measurable concentration (tlast) will be derived from the pharmacokinetic (PK) serum samples collected.

  20. Pharmacokinetics (PK) of ASP1948 in serum: CL [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Total clearance after intravenous dosing (CL) will be derived from the pharmacokinetic (PK) serum samples collected.

  21. Pharmacokinetics (PK) of ASP1948 in serum: Vz [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Volume of distribution after intravenous dosing during the terminal elimination phase (Vz) will be derived from the pharmacokinetic (PK) serum samples collected.

  22. Pharmacokinetics (PK) of ASP1948 in serum: Vss [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Volume of distribution at steady state after intravenous dosing (Vss) will be derived from the pharmacokinetic (PK) serum samples collected.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 and modified RECIST 1.1 for immune-based therapeutics (iRECIST) [ Time Frame: Up to a maximum of 93 weeks ]
    Initial and retreatment. ORR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed complete response (CR) or partial response (PR).

  2. Duration of Response (DOR) per RECIST V1.1 and iRECIST [ Time Frame: Up to a maximum of 93 weeks ]
    Initial and retreatment. DOR is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression/death or date of censoring

  3. Persistence of response after discontinuation per RECIST V1.1 and iRECIST [ Time Frame: Up to a maximum of 93 weeks ]
    Initial and retreatment. Persistence of response is defined as the time from the date of treatment discontinuation to the date of radiographical progression or date of censoring.

  4. Disease Control Rate (DCR) per RECIST V1.1 and iRECIST [ Time Frame: Up to a maximum of 93 weeks ]
    Initial and retreatment. DCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed CR, PR or stable disease (SD).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject has locally-advanced (unresectable) or metastatic solid tumor malignancy (no limit to the number of prior treatment regimens) that is confirmed by available pathology records or current biopsy, and has received all standard therapies (unless the therapy is contraindicated or intolerable) felt to provide clinical benefit.
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  • Subject's last dose of prior antineoplastic therapy, including any immunotherapy, was at least 21 days prior to initiation of study drug administration. A subject with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is allowed to remain on EGFR tyrosine kinase inhibitor (TKI) therapy until 4 days prior to the start of study drug administration.
  • Subject has completed any radiotherapy (including stereotactic radiosurgery) at least 14 days prior to study drug administration.
  • Subject with metastatic castration-resistant prostate cancer (mCRPC) (positive scan and/or soft tissue disease documented by computed tomography/magnetic resonance imaging) meets both of the following:

    • Subject has serum testosterone ≤ 50 ng/dL at screening.
    • Subject has had an orchiectomy or plans to continue androgen deprivation therapy (ADT) for the duration of study treatment.
  • Subject has adequate organ function as indicated by laboratory values. (If a subject has received a recent blood transfusion, the laboratory tests must be obtained ≥ 28 days after any blood transfusion.)
  • Female subject must either:

    • Be of non-childbearing potential: post-menopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or; documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy).
    • Or, if of childbearing potential: Agree not to try to become pregnant during the study treatment and for 6 months after the final study drug administration; and have a negative urine or serum pregnancy test prior to study drug administration; and if heterosexually active, agree to consistently use 1 form of highly effective birth control starting at screening and throughout the study treatment and 6 months after the final study drug administration.
  • Female subject must agree not to breastfeed starting at screening and throughout the study treatment, and for 6 months after the final study drug administration.
  • Female subject must not donate ova starting at screening and throughout the study treatment, and for 6 months after the final study drug administration.
  • A sexually active male subject with female partner(s) who are of childbearing potential is eligible if :

    • The male subject agrees to use a male condom starting at screening and continues throughout the study treatment, and for 6 months after the final study drug administration.
    • The male subject has not had a vasectomy or is not sterile, as defined below and the subject's female partner(s) is utilizing 1 form of highly effective birth control starting at screening and continuing throughout the study treatment and for 6 months after the final study drug administration.
  • Male subject must not donate sperm starting at screening and throughout the study treatment, and for 6 months after the final study drug administration.
  • Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study treatment and for 6 months after the final study drug administration.
  • Subject agrees not to participate in another interventional study while receiving study drug (subjects who are currently in the follow-up period of an interventional clinical trial are allowed).

Additional Inclusion Criteria for Subjects in the Expansion Cohorts:

  • Subject has at least 1 measureable lesion per RECIST 1.1. The measureable lesion must be outside the field of radiation if subject had prior radiotherapy. Subjects with mCRPC who do not have measurable lesions must have at least 1 of the following:

    • Progression with 2 or more new bone lesions, or
    • Prostate specific antigen (PSA) progression (defined as a minimum of 3 rising PSA levels with an interval of ≥ 1 week between each determination) within 6 weeks prior to study drug administration and a PSA value at the screening visit ≥ 2 ng/mL.
  • Subject consents to provide available tumor specimen in a tissue block or unstained serial slides obtained within 8 to 56 days prior to first dose of study treatment.
  • Subject with squamous cell carcinoma of the head and neck (SCCHN), melanoma and breast cancer, is an appropriate candidate for tumor biopsy and consents to undergoing a tumor biopsy (core needle biopsy or excision) during the treatment period.

Additional Inclusion Criteria for Re-treatment:

Subjects may be eligible for study drug re-treatment if the study remains open and the subject continues to meet all of the eligibility criteria above (except prior use of this drug) and the following conditions:

  • Subject stopped initial treatment with ASP1948 after attaining a confirmed CR or PR or SD.
  • Subject experienced a confirmed disease progression by iRECIST (iCPD) (or unconfirmed progressive disease by iRECIST (iUPD) if subject is not clinically stable to await confirmatory scan) after stopping the subjects initial treatment with ASP1948.
  • Subject did not receive any prohibited anti-cancer treatment since the last dose of ASP1948.
  • Subject did not experience a toxicity that met the discontinuation criteria during the initial treatment with ASP1948.

Exclusion Criteria:

  • Subject weighs < 45 kg.
  • Subject has received investigational therapy (other than an investigational epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in a subject with EGFR mutations) within 21 days prior to start of study drug.
  • Subject requires or has received systemic steroid therapy or any other immunosuppressive therapy within 14 days prior to study drug administration. Subjects using a physiologic replacement dose of hydrocortisone or its equivalent(defined as up to 30 mg per day of hydrocortisone, 2 mg per day of dexamethasone or up to 10 mg per day of prednisone) are allowed.
  • Subject has symptomatic central nervous system (CNS) metastases or subject has evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans). Subjects with previously treated CNS metastases are eligible, if the subject is clinically stable and has no evidence of CNS progression by imaging for at least 28 days prior to start of study treatment and are not requiring immunosuppressive doses of systemic steroids (> 30 mg per day of hydrocortisone, > 2 mg per day of dexamethasone or > 10 mg per day of prednisone or equivalent) for longer than 14 days.
  • Subject has leptomeningeal disease as a manifestation of the current malignancy.
  • Subject has an active autoimmune disease. Subjects with type 1 diabetes mellitus, stable endocrinopathies maintained on appropriate replacement therapy and skin disorders (e.g., vitiligo, psoriasis or alopecia) not requiring systemic treatment are allowed.
  • Subject was discontinued from prior immunomodulatory therapy due to a Grade ≥ 3 toxicity that was mechanistically related (e.g., immune related) to the agent.
  • Subject has known history of serious hypersensitivity reaction to a known ingredient of ASP1948 or severe hypersensitivity reaction to treatment with another monoclonal antibody.
  • Subject with positive Hepatitis B virus antibodies and surface antigen (indicating acute Hepatitis B virus (HBV) or chronic HBV) or Hepatitis C (HCV ribonucleic acid (RNA) (qualitative); subject with negative Hepatitis C antibody testing may not need RNA testing.
  • Subject has received a live vaccine against infectious diseases within 28 days prior to initiation of study treatment.
  • Subject has a history of drug-induced pneumonitis (interstitial lung disease) or currently has pneumonitis.
  • Subject has an active infection requiring systemic therapy (e.g., intravenous antibiotics) within 14 days prior to study drug treatment.
  • Subject is expected to require another form of antineoplastic therapy while on study treatment.
  • Subject has an uncontrolled intercurrent illness including, but not limited to cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements.
  • Subject's AEs (excluding alopecia) from prior therapy have not improved to Grade 1 or baseline within 14 days prior to start of study treatment.
  • Subject has significant cardiovascular disease including:

    • Subject has inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications).
    • Subject has a history of myocardial infarction or unstable angina within 6 months prior to day 1.
    • Subject has New York Heart Association Class II or greater chronic heart failure (CHF).
    • History of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to study treatment.
    • Subject has significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to study treatment.
  • Subject has a history of hemoptysis (bright red blood of ½ teaspoon or more per episode) within 12 weeks prior to study treatment.
  • Subject has evidence of a bleeding diathesis or significant coagulopathy.
  • Subject has inadequate recovery from prior surgical procedure or has had a major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to day 1, or anticipates the need for a major surgical procedure during the course of the study or minor surgery within 7 days of starting study treatment.
  • Subject has received treatment with medications that affect the coagulation cascade with an international normalized ratio (INR) ≥ 2 such as vitamin K antagonists, heparins and direct thrombin inhibitors or the use of factor Xa inhibitors within 28 days prior to the start of study treatment.
  • Subject has any condition that makes the subject unsuitable for study participation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03565445


Contacts
Contact: Astellas Pharma Global Development, Inc. 800-888-7704 astellas.registration@astellas.com

Locations
United States, Connecticut
Yale Center for Clinical Investigation Recruiting
New Haven, Connecticut, United States, 06520-8028
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89169
United States, Tennessee
Sarah Cannon Research Institute - SCRI Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
South Texas Accelerated Research Therapeutics Recruiting
San Antonio, Texas, United States, 78229
United States, Virginia
Virginia Cancer Care Specialist, PC Recruiting
Fairfax, Virginia, United States, 22031
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Potenza Therapeutics
Investigators
Study Director: Medical Monitor Astellas Pharma Global Development, Inc.

Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT03565445     History of Changes
Other Study ID Numbers: 1948-CL-0101
First Posted: June 21, 2018    Key Record Dates
Last Update Posted: October 31, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
NSCLC
Tumors
squamous cell carcinoma of the head and neck (SCCHN)
Oncology
breast cancer
ASP1948
mCRPC
melanoma
ovarian cancer
Locally advanced or metastatic solid tumor malignancies
Advanced solid tumors

Additional relevant MeSH terms:
Neoplasms