<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04434482</url>
  </required_header>
  <id_info>
    <org_study_id>IMP4297-106</org_study_id>
    <nct_id>NCT04434482</nct_id>
  </id_info>
  <brief_title>IMP4297 in Combination With Temozolomide in Patients With Advanced Solid Tumors and Small Cell Lung Cancer</brief_title>
  <official_title>A Phase Ib/II, Open-Label, Multi-Center, Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of IMP4297 in Combination With Temozolomide in Patients With Advanced Solid Tumors and Small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Impact Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Impact Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, multi-center, dose-escalation and dose-expansion phase I study to&#xD;
      evaluate the safety, tolerability, PK characteristics and anti-tumor activity of PARP&#xD;
      inhibitor IMP4297 and temozolomide combination therapy in patients with advanced solid tumors&#xD;
      and with ES-SCLC who develops disease progression after 1L platinum-based regimen.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will be conducted in two parts. Part I of the study will be dose escalation&#xD;
      evaluation to determine the MTD and/or RP2D of IMP4297 in combination with temozolomide. Part&#xD;
      II of the study will be conducted in two RP2D expansion cohorts (sensitive ES-SCLC cohort and&#xD;
      resistant ES-SCLC cohort) to further evaluate the anti-tumor activity, safety and&#xD;
      tolerability of this regimen in ES-SCLC patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 7, 2020</start_date>
  <completion_date type="Anticipated">January 2023</completion_date>
  <primary_completion_date type="Anticipated">October 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety endpoints</measure>
    <time_frame>6 months</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by NCI CTCAE v5.0.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MTD</measure>
    <time_frame>Within 28 days after IMP4297 and temozolomide administrated</time_frame>
    <description>the maximum tolerated dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>RP2D</measure>
    <time_frame>Within 28 days after IMP4297 and temozolomide administrated</time_frame>
    <description>the recommended phase 2 dose</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>plasma PK profile</measure>
    <time_frame>6 months</time_frame>
    <description>To characterize the plasma PK profile of IMP4297 and temozolomide via population PK (popPK) modeling</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>anti-tumor activity</measure>
    <time_frame>6 months</time_frame>
    <description>To evaluate the preliminary anti-tumor activity of IMP4297 in combination with temozolomide</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">113</enrollment>
  <condition>Advanced Solid Tumours</condition>
  <condition>Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>IMP4297 and temozolomide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IMP4297 and temozolomide&#xD;
The dose levels will be escalated following a modified 3+3 dose escalation scheme.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IMP4297</intervention_name>
    <description>The dose levels will be escalated following a modified 3+3 dose escalation scheme.</description>
    <arm_group_label>IMP4297 and temozolomide</arm_group_label>
    <other_name>temozolomide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The patient must voluntarily participate in this clinical study and be willing and&#xD;
             able to provide written informed consent/assent for the trial.&#xD;
&#xD;
          2. Age ≥ 18 years old on the day of signing informed consent form (ICF), males or females&#xD;
&#xD;
          3. Patient population:&#xD;
&#xD;
               1. In Part I: The patient must have histologically or cytologically confirmed&#xD;
                  advanced solid tumor that is refractory to standard treatment or for which no&#xD;
                  standard treatment exists, including but not limited to triple-negative breast&#xD;
                  cancer (TNBC), SCLC, ovarian cancer (OC) and metastatic castration-resistant&#xD;
                  prostate cancer (mCRPC).&#xD;
&#xD;
               2. In Part II: The patients must be histologically or cytologically confirmed&#xD;
                  ES-SCLC with disease progression after one and only one course of 1L standard&#xD;
                  platinum-based therapy. Anti-PD-1 or anti-PD-L1 antibody therapy is acceptable as&#xD;
                  long as it's part of the 1L treatment. Including platinum sensitive and platinum&#xD;
                  resistant patients. Platinum sensitive is defined as the relapse-free interval&#xD;
                  exceeds 90 days after treatment with platinum doublets is completed; The platinum&#xD;
                  resistant represents disease relapses within 90 days of treatment completion&#xD;
                  during a chemotherapy-free interval (CFI).&#xD;
&#xD;
               3. In Part I: Patients have an ECOG performance status of 0 to 1.&#xD;
&#xD;
               4. In Part II: Patients have an ECOG performance status of 0 to 2.&#xD;
&#xD;
               5. Patients have a life expectancy of ≥12 weeks.&#xD;
&#xD;
               6. In Part II: patients have at least 1 measurable lesion per RECIST v1.1, including&#xD;
                  a previously irradiated lesion if has progressed since radiotherapy, that can be&#xD;
                  accurately measured at baseline which is suitable for accurate repeated&#xD;
                  measurements&#xD;
&#xD;
          4. Patients have adequate organ function, as indicated by the following laboratory values&#xD;
             (had not received blood transfusion, apheresis infusion, erythropoietin, granulocyte&#xD;
             colony-stimulating factor, and other relevant medical support within 28 days before&#xD;
             the administration of the IPs&#xD;
&#xD;
          5. Female patients should meet at least 1 of the following criteria before they can&#xD;
             participate in the study:&#xD;
&#xD;
               -  Females who have no childbearing potential (i.e., physiologically incapable of&#xD;
                  pregnancy), including those who have undergone hysterectomy, bilateral&#xD;
                  oophorectomy, or bilateral salpingectomy.&#xD;
&#xD;
               -  Post-menopausal (total cessation of menses for ≥1 year).&#xD;
&#xD;
               -  For those with childbearing potential, they should have a negative serum&#xD;
                  pregnancy test during the screening period (within 7 days prior to the first dose&#xD;
                  of the IPs), should not be in lactation, and willing to take effective&#xD;
                  contraceptive measures throughout the study period, from study entry up to 6&#xD;
                  months after the last dose of the IP(s).&#xD;
&#xD;
          6. Male patients are eligible to participate in the study if they have undergone&#xD;
             vasectomy or agree to use effective methods of contraception from study entry up to 6&#xD;
             months after the last dose of the IP(s).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with primary tumor in central nervous system (CNS) and active or untreated&#xD;
             central CNS metastases and/or carcinomatous meningitis should be excluded. Patients&#xD;
             with previously treated brain metastases may participate provided they are clinically&#xD;
             stable for at least 4 weeks and, have no evidence of new or enlarging brain metastases&#xD;
             and no requirements for corticosteroids 14 days prior to dosing with IPs.&#xD;
&#xD;
          2. Patients with serious acute and chronic infections, including:&#xD;
&#xD;
               -  Patients with an uncontrolled acute infection, or an active infection requiring&#xD;
                  systemic treatment, or patients who have received systemic antibiotics within 2&#xD;
                  weeks prior to the first dose of the IPs; prophylaxis use of systemic antibiotics&#xD;
                  treatment for upper tract infection is allowed as long as no violation with the&#xD;
                  requirement in Section 6.5 Concomitant Therapy.&#xD;
&#xD;
               -  Patients who have a known history of human immunodeficiency virus (HIV) infection&#xD;
                  and/or acquired immunodeficiency syndrome or positive HIV testing should undergo&#xD;
                  CD4+ T-cell test during the screening period. Patients with CD4+ T-cell counts &lt;&#xD;
                  350 cells/uL are ineligible for enrollment. Patients with unknown HIV infection&#xD;
                  status who are unwilling to undergo HIV testing should not be enrolled in the&#xD;
                  study;&#xD;
&#xD;
               -  Patients who have known active hepatitis B or C. To be included in the study,&#xD;
                  patients with hepatitis B virus surface antigen (HBsAg) or hepatitis C virus&#xD;
                  (HCV) antibody positive test results during screening must be further tested for&#xD;
                  hepatitis B virus (HBV) DNA titer (excluding patients with a DNA titer of more&#xD;
                  than 2500 copies [cps]/mL or 500 IU/mL) and HCV RNA (excluding patients with an&#xD;
                  HCV RNA concentration exceeding the lower detection limit of the assay) to&#xD;
                  exclude active hepatitis B or hepatitis C infection requiring treatment.&#xD;
                  Hepatitis B virus carriers, patients with stable hepatitis B infection after drug&#xD;
                  treatment (DNA titer not exceeding 2500 copies [cps]/mL or 500 IU/mL) and&#xD;
                  hepatitis C infected patients who received treatment and achieved sustained&#xD;
                  virologic response for at least 12 weeks can be enrolled.&#xD;
&#xD;
               -  Note: If the lower detection limit of the HBV DNA assay in the study centers is&#xD;
                  higher than 2500 copies [cps]/mL or 500 IU/mL, the patients in the study center&#xD;
                  with an HBV DNA assay result lower than the lower detection limit of the assay&#xD;
                  can be enrolled.&#xD;
&#xD;
               -  Active tuberculosis&#xD;
&#xD;
          3. Patients who have previously received PARP inhibitors.&#xD;
&#xD;
          4. Patients who have received strong CYP3A4 inhibitors or inducers prior to the first&#xD;
             dose of the IPs (the patient can be enrolled if the elution period prior to the first&#xD;
             dose of the IPs is ≥5 half-lives), or patients who need to continue receiving these&#xD;
             medications during the study period.&#xD;
&#xD;
          5. Patients who have received a live-virus vaccination within 28 days of the planned&#xD;
             start of study.&#xD;
&#xD;
          6. Patients who have participated a study of an investigational agent and received study&#xD;
             therapy or used an investigational device within 28 days of the first dose of&#xD;
             treatment.&#xD;
&#xD;
          7. Patients have not recovered (i.e., to ≤Grade 1 or to baseline, as evaluated by&#xD;
             NCI-CTCAE v5.0) from cytotoxic therapy-induced AEs, except for alopecia.&#xD;
&#xD;
          8. Patients who have received anti-cancer chemotherapy, endocrine therapy,&#xD;
             herbal/alternative therapies (including Chinese herbal or Chinese medicine or&#xD;
             proprietary Chinese medicine), or other anti-cancer systemic treatment (except&#xD;
             anti-cancer antibody) within 5 half-lives or 14 days, whichever is longer prior to the&#xD;
             first dose of the IPs. Patients who have received anti-cancer antibody within 28 days&#xD;
             prior to the first dose of the IPs.&#xD;
&#xD;
          9. Patients who have undergone a major surgery within 28 days prior to the study&#xD;
             treatment, or have undergone a radical radiotherapy, or have undergone a palliative&#xD;
             radiotherapy within 14 days prior to the study treatment, or have used a radioactive&#xD;
             drug (Strontium, Samarium, etc.) within 56 days prior to the study treatment.&#xD;
&#xD;
         10. In Part II of the study, patients who have other malignancies within 2 years prior to&#xD;
             the first dose of the IPs will be excluded. except for radically treated locally&#xD;
             curable malignant tumors, such as basal or squamous cell skin cancer, superficial&#xD;
             bladder cancer, or prostate, cervical or breast carcinoma in situ.&#xD;
&#xD;
         11. Patients with uncontrolled pleural effusion, pericardial effusion or ascites requiring&#xD;
             recurrent drainage procedures (once monthly or more frequently). Please contact&#xD;
             medical monitor if any further discussion or clarification is needed.&#xD;
&#xD;
         12. Patients with a history of seizures.&#xD;
&#xD;
         13. Patients with a previously documented diagnosis of myelodysplastic syndrome (MDS).&#xD;
&#xD;
         14. Patients who have major cardiovascular diseases (such as congestive heart failure,&#xD;
             unstable angina, atrial fibrillation, arrhythmia); patients who have acute myocardial&#xD;
             infarction, unstable angina, stroke, or transient ischemic attack within 6 months&#xD;
             prior to the first dose of the IPs; patients who have congestive heart failure (≥New&#xD;
             York Heart Association [NYHA] Classification Class II); patients who have severe&#xD;
             arrhythmia requiring medication (including QT interval [QTc] prolongation corrected by&#xD;
             the Fridericia's formula [QTcF] of more than 480 msec, pacemaker installation, and&#xD;
             previous diagnosis of congenital long QT syndrome).&#xD;
&#xD;
         15. Patients who are unable to swallow capsules. Patients have gastrointestinal illnesses&#xD;
             that may affect the absorption of oral medication IMP4297 and temozolomide.&#xD;
&#xD;
         16. Patients with a known hypersensitivity to IMP4297, temozolomide or any of the&#xD;
             excipients of the products.&#xD;
&#xD;
         17. Patients who have received transplantation including patients with previous allogeneic&#xD;
             bone marrow transplant.&#xD;
&#xD;
         18. Patients known to have a history of alcoholism or drug abuse.&#xD;
&#xD;
         19. The investigator believes that the patient's underlying disease may put the patient at&#xD;
             risk in IP administration or may affect the evaluation of toxicity events or AEs.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Bitao Z Sarapa</last_name>
    <phone>+1 (908) 303-2808</phone>
    <email>bitao.sarapa@impacttherapeutics.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Border Medical Centre</name>
      <address>
        <city>Albury</city>
        <state>New South Wales</state>
        <zip>2640</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Debbie Metcalf</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Blacktown Hospital</name>
      <address>
        <city>Blacktown</city>
        <state>New South Wales</state>
        <zip>2148</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Grace Murray</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Orange Hospital</name>
      <address>
        <city>Orange</city>
        <state>New South Wales</state>
        <zip>2800</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Carol Han</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Peninsula Health</name>
      <address>
        <city>Frankston</city>
        <state>Victoria</state>
        <zip>3199</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Linda Raineri</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Chungbuk National University Hospital</name>
      <address>
        <city>Cheongju-si</city>
        <zip>2864</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Yun So Yun Yun</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Catholic university of Korea, st. Vincent's Hospital</name>
      <address>
        <city>Gyeonggi-do</city>
        <zip>16247</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jung Soon Kim</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Yonsei university health system, Severance Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lee Seul Gi</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Kang Yoonsook</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>China Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <zip>404</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pei-Chen Hsu</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital</name>
      <address>
        <city>Tainan</city>
        <zip>704</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Hsiang-Lien Li</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Chi Mei Medical Center</name>
      <address>
        <city>Tainan</city>
        <zip>73657</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lillian Lee</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Chang Gung Medical Foundation Linko</name>
      <address>
        <city>Taoyuan</city>
        <zip>333</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Korea, Republic of</country>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>June 14, 2020</study_first_submitted>
  <study_first_submitted_qc>June 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 17, 2020</study_first_posted>
  <last_update_submitted>August 10, 2021</last_update_submitted>
  <last_update_submitted_qc>August 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Small Cell Lung Carcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Temozolomide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04434482
org study id: IMP4297-106
nct id: NCT04434482
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is an open-label, multi-center, dose-escalation and dose-expansion phase I study to
      evaluate the safety, tolerability, PK characteristics and anti-tumor activity of PARP
      inhibitor IMP4297 and temozolomide combination therapy in patients with advanced solid tumors
      and with ES-SCLC who develops disease progression after 1L platinum-based regimen.
This study will be conducted in two parts. Part I of the study will be dose escalation
      evaluation to determine the MTD and/or RP2D of IMP4297 in combination with temozolomide. Part
      II of the study will be conducted in two RP2D expansion cohorts (sensitive ES-SCLC cohort and
      resistant ES-SCLC cohort) to further evaluate the anti-tumor activity, safety and
      tolerability of this regimen in ES-SCLC patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety endpoints
time frame: 6 months
description: Number of participants with treatment-related adverse events as assessed by NCI CTCAE v5.0.
measure: MTD
time frame: Within 28 days after IMP4297 and temozolomide administrated
description: the maximum tolerated dose
measure: RP2D
time frame: Within 28 days after IMP4297 and temozolomide administrated
description: the recommended phase 2 dose
measure: plasma PK profile
time frame: 6 months
description: To characterize the plasma PK profile of IMP4297 and temozolomide via population PK (popPK) modeling
measure: anti-tumor activity
time frame: 6 months
description: To evaluate the preliminary anti-tumor activity of IMP4297 in combination with temozolomide
arm group label: IMP4297 and temozolomide
arm group type: Experimental
description: IMP4297 and temozolomide
The dose levels will be escalated following a modified 3+3 dose escalation scheme.
intervention type: Drug
intervention name: IMP4297
description: The dose levels will be escalated following a modified 3+3 dose escalation scheme.
arm group label: IMP4297 and temozolomide
other name: temozolomide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bitao Z Sarapa
phone: +1 (908) 303-2808
email: bitao.sarapa@impacttherapeutics.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
facility: 
status: Not yet recruiting
country: Australia
country: Korea, Republic of
country: Taiwan
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Small Cell Lung Carcinoma
mesh term: Temozolomide
sharing ipd: No