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IMP4297 in Combination With Temozolomide in Patients With Advanced Solid Tumors and Small Cell Lung Cancer

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. Identifier: NCT04434482
Recruitment Status : Recruiting
First Posted : June 17, 2020
Last Update Posted : August 17, 2021
Information provided by (Responsible Party):
Impact Therapeutics, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumours Small Cell Lung Cancer Drug: IMP4297 Phase 1

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 113 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 7, 2020
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : January 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: IMP4297 and temozolomide

IMP4297 and temozolomide

The dose levels will be escalated following a modified 3+3 dose escalation scheme.

Drug: IMP4297
The dose levels will be escalated following a modified 3+3 dose escalation scheme.
Other Name: temozolomide

Primary Outcome Measures :
  1. Safety endpoints [ Time Frame: 6 months ]
    Number of participants with treatment-related adverse events as assessed by NCI CTCAE v5.0.

  2. MTD [ Time Frame: Within 28 days after IMP4297 and temozolomide administrated ]
    the maximum tolerated dose

  3. RP2D [ Time Frame: Within 28 days after IMP4297 and temozolomide administrated ]
    the recommended phase 2 dose

Secondary Outcome Measures :
  1. plasma PK profile [ Time Frame: 6 months ]
    To characterize the plasma PK profile of IMP4297 and temozolomide via population PK (popPK) modeling

  2. anti-tumor activity [ Time Frame: 6 months ]
    To evaluate the preliminary anti-tumor activity of IMP4297 in combination with temozolomide

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.

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

Inclusion Criteria:

  1. The patient must voluntarily participate in this clinical study and be willing and able to provide written informed consent/assent for the trial.
  2. Age ≥ 18 years old on the day of signing informed consent form (ICF), males or females
  3. Patient population:

    1. In Part I: The patient must have histologically or cytologically confirmed advanced solid tumor that is refractory to standard treatment or for which no standard treatment exists, including but not limited to triple-negative breast cancer (TNBC), SCLC, ovarian cancer (OC) and metastatic castration-resistant prostate cancer (mCRPC).
    2. In Part II: The patients must be histologically or cytologically confirmed ES-SCLC with disease progression after one and only one course of 1L standard platinum-based therapy. Anti-PD-1 or anti-PD-L1 antibody therapy is acceptable as long as it's part of the 1L treatment. Including platinum sensitive and platinum resistant patients. Platinum sensitive is defined as the relapse-free interval exceeds 90 days after treatment with platinum doublets is completed; The platinum resistant represents disease relapses within 90 days of treatment completion during a chemotherapy-free interval (CFI).
    3. In Part I: Patients have an ECOG performance status of 0 to 1.
    4. In Part II: Patients have an ECOG performance status of 0 to 2.
    5. Patients have a life expectancy of ≥12 weeks.
    6. In Part II: patients have at least 1 measurable lesion per RECIST v1.1, including a previously irradiated lesion if has progressed since radiotherapy, that can be accurately measured at baseline which is suitable for accurate repeated measurements
  4. Patients have adequate organ function, as indicated by the following laboratory values (had not received blood transfusion, apheresis infusion, erythropoietin, granulocyte colony-stimulating factor, and other relevant medical support within 28 days before the administration of the IPs
  5. Female patients should meet at least 1 of the following criteria before they can participate in the study:

    • Females who have no childbearing potential (i.e., physiologically incapable of pregnancy), including those who have undergone hysterectomy, bilateral oophorectomy, or bilateral salpingectomy.
    • Post-menopausal (total cessation of menses for ≥1 year).
    • For those with childbearing potential, they should have a negative serum pregnancy test during the screening period (within 7 days prior to the first dose of the IPs), should not be in lactation, and willing to take effective contraceptive measures throughout the study period, from study entry up to 6 months after the last dose of the IP(s).
  6. Male patients are eligible to participate in the study if they have undergone vasectomy or agree to use effective methods of contraception from study entry up to 6 months after the last dose of the IP(s).

Exclusion Criteria:

  1. Patients with primary tumor in central nervous system (CNS) and active or untreated central CNS metastases and/or carcinomatous meningitis should be excluded. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks and, have no evidence of new or enlarging brain metastases and no requirements for corticosteroids 14 days prior to dosing with IPs.
  2. Patients with serious acute and chronic infections, including:

    • Patients with an uncontrolled acute infection, or an active infection requiring systemic treatment, or patients who have received systemic antibiotics within 2 weeks prior to the first dose of the IPs; prophylaxis use of systemic antibiotics treatment for upper tract infection is allowed as long as no violation with the requirement in Section 6.5 Concomitant Therapy.
    • Patients who have a known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome or positive HIV testing should undergo CD4+ T-cell test during the screening period. Patients with CD4+ T-cell counts < 350 cells/uL are ineligible for enrollment. Patients with unknown HIV infection status who are unwilling to undergo HIV testing should not be enrolled in the study;
    • Patients who have known active hepatitis B or C. To be included in the study, patients with hepatitis B virus surface antigen (HBsAg) or hepatitis C virus (HCV) antibody positive test results during screening must be further tested for hepatitis B virus (HBV) DNA titer (excluding patients with a DNA titer of more than 2500 copies [cps]/mL or 500 IU/mL) and HCV RNA (excluding patients with an HCV RNA concentration exceeding the lower detection limit of the assay) to exclude active hepatitis B or hepatitis C infection requiring treatment. Hepatitis B virus carriers, patients with stable hepatitis B infection after drug treatment (DNA titer not exceeding 2500 copies [cps]/mL or 500 IU/mL) and hepatitis C infected patients who received treatment and achieved sustained virologic response for at least 12 weeks can be enrolled.
    • Note: If the lower detection limit of the HBV DNA assay in the study centers is higher than 2500 copies [cps]/mL or 500 IU/mL, the patients in the study center with an HBV DNA assay result lower than the lower detection limit of the assay can be enrolled.
    • Active tuberculosis
  3. Patients who have previously received PARP inhibitors.
  4. Patients who have received strong CYP3A4 inhibitors or inducers prior to the first dose of the IPs (the patient can be enrolled if the elution period prior to the first dose of the IPs is ≥5 half-lives), or patients who need to continue receiving these medications during the study period.
  5. Patients who have received a live-virus vaccination within 28 days of the planned start of study.
  6. Patients who have participated a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of treatment.
  7. Patients have not recovered (i.e., to ≤Grade 1 or to baseline, as evaluated by NCI-CTCAE v5.0) from cytotoxic therapy-induced AEs, except for alopecia.
  8. Patients who have received anti-cancer chemotherapy, endocrine therapy, herbal/alternative therapies (including Chinese herbal or Chinese medicine or proprietary Chinese medicine), or other anti-cancer systemic treatment (except anti-cancer antibody) within 5 half-lives or 14 days, whichever is longer prior to the first dose of the IPs. Patients who have received anti-cancer antibody within 28 days prior to the first dose of the IPs.
  9. Patients who have undergone a major surgery within 28 days prior to the study treatment, or have undergone a radical radiotherapy, or have undergone a palliative radiotherapy within 14 days prior to the study treatment, or have used a radioactive drug (Strontium, Samarium, etc.) within 56 days prior to the study treatment.
  10. In Part II of the study, patients who have other malignancies within 2 years prior to the first dose of the IPs will be excluded. except for radically treated locally curable malignant tumors, such as basal or squamous cell skin cancer, superficial bladder cancer, or prostate, cervical or breast carcinoma in situ.
  11. Patients with uncontrolled pleural effusion, pericardial effusion or ascites requiring recurrent drainage procedures (once monthly or more frequently). Please contact medical monitor if any further discussion or clarification is needed.
  12. Patients with a history of seizures.
  13. Patients with a previously documented diagnosis of myelodysplastic syndrome (MDS).
  14. Patients who have major cardiovascular diseases (such as congestive heart failure, unstable angina, atrial fibrillation, arrhythmia); patients who have acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to the first dose of the IPs; patients who have congestive heart failure (≥New York Heart Association [NYHA] Classification Class II); patients who have severe arrhythmia requiring medication (including QT interval [QTc] prolongation corrected by the Fridericia's formula [QTcF] of more than 480 msec, pacemaker installation, and previous diagnosis of congenital long QT syndrome).
  15. Patients who are unable to swallow capsules. Patients have gastrointestinal illnesses that may affect the absorption of oral medication IMP4297 and temozolomide.
  16. Patients with a known hypersensitivity to IMP4297, temozolomide or any of the excipients of the products.
  17. Patients who have received transplantation including patients with previous allogeneic bone marrow transplant.
  18. Patients known to have a history of alcoholism or drug abuse.
  19. The investigator believes that the patient's underlying disease may put the patient at risk in IP administration or may affect the evaluation of toxicity events or AEs.

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 identifier (NCT number): NCT04434482

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Contact: Bitao Z Sarapa +1 (908) 303-2808

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Australia, New South Wales
Border Medical Centre Recruiting
Albury, New South Wales, Australia, 2640
Contact: Debbie Metcalf         
Blacktown Hospital Recruiting
Blacktown, New South Wales, Australia, 2148
Contact: Grace Murray         
Orange Hospital Recruiting
Orange, New South Wales, Australia, 2800
Contact: Carol Han         
Australia, Victoria
Peninsula Health Not yet recruiting
Frankston, Victoria, Australia, 3199
Contact: Linda Raineri         
Korea, Republic of
Chungbuk National University Hospital Not yet recruiting
Cheongju-si, Korea, Republic of, 2864
Contact: Yun So Yun Yun         
The Catholic university of Korea, st. Vincent's Hospital Recruiting
Gyeonggi-do, Korea, Republic of, 16247
Contact: Jung Soon Kim         
Yonsei university health system, Severance Hospital Not yet recruiting
Seoul, Korea, Republic of, 03722
Contact: Lee Seul Gi         
Asan Medical Center Not yet recruiting
Seoul, Korea, Republic of, 05505
Contact: Kang Yoonsook         
China Medical University Hospital Recruiting
Taichung, Taiwan, 404
Contact: Pei-Chen Hsu         
National Cheng Kung University Hospital Not yet recruiting
Tainan, Taiwan, 704
Contact: Hsiang-Lien Li         
Chi Mei Medical Center Recruiting
Tainan, Taiwan, 73657
Contact: Lillian Lee         
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Chang Gung Medical Foundation Linko Not yet recruiting
Taoyuan, Taiwan, 333
Sponsors and Collaborators
Impact Therapeutics, Inc.
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Responsible Party: Impact Therapeutics, Inc. Identifier: NCT04434482    
Other Study ID Numbers: IMP4297-106
First Posted: June 17, 2020    Key Record Dates
Last Update Posted: August 17, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents