Clinical Trials /

Study of CYH33 in Combination With Olaparib an Oral PARP Inhibitor in Patients With Advanced Solid Tumors.

NCT04586335

Description:

The purpose of this study is to assess the safety, tolerability and preliminary efficacy of CYH33 in combination with olaprib in patients with DDR gene mutations and/or PIK3CA mutations, in patients who have progressed on prior PARP inhibitor, and in patients with recurrent high grade serous ovarian, fallopian tube, or primary peritoneal cancer who are platinum resistant or refractory. The study will assess if this combination will optimize anti-tumor activity, block tumor growth and overcome the resistance to PARP inhibitor treatment. The study consists 2 parts. In Part 1 dose escalation, the objective is to determine the maximum toleration dose (MTD) of the combination. The final recommended phase 2 dose (RP2D) of CYH33 in combination with olaparib will be based on the totality of an overall assessment of available safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy which could be the MTD or a dose level lower in specific cohorts of patients. In Part 2 dose expansion, the main objective is to evaluate the efficacy at RP2D.

Related Conditions:
  • High Grade Fallopian Tube Serous Adenocarcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Malignant Solid Tumor
  • Primary Peritoneal High Grade Serous Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of CYH33, an Oral α-specific PI3K Inhibitor in Combination With Olaparib an Oral PARP Inhibitor in Patients With Advanced Solid Tumors.
  • Official Title: Open Label, Phase Ib Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of CYH33, an Oral α-specific PI3K Inhibitor in Combination With Olaparib, an Oral PARP Inhibitor in Patients With Advanced Solid Tumors.

Clinical Trial IDs

  • ORG STUDY ID: CYH33-G102
  • NCT ID: NCT04586335

Conditions

  • Ovarian Cancer
  • Breast Cancer
  • Solid Tumor
  • Prostate Cancer
  • Endometrial Cancer

Interventions

DrugSynonymsArms
CYH33CYH33 in Combination with Olaparib

Purpose

The purpose of this study is to assess the safety, tolerability and preliminary efficacy of CYH33 in combination with olaprib in patients with DDR gene mutations and/or PIK3CA mutations, in patients who have progressed on prior PARP inhibitor, and in patients with recurrent high grade serous ovarian, fallopian tube, or primary peritoneal cancer who are platinum resistant or refractory. The study will assess if this combination will optimize anti-tumor activity, block tumor growth and overcome the resistance to PARP inhibitor treatment. The study consists 2 parts. In Part 1 dose escalation, the objective is to determine the maximum toleration dose (MTD) of the combination. The final recommended phase 2 dose (RP2D) of CYH33 in combination with olaparib will be based on the totality of an overall assessment of available safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy which could be the MTD or a dose level lower in specific cohorts of patients. In Part 2 dose expansion, the main objective is to evaluate the efficacy at RP2D.

Detailed Description

      DNA damage repair (DDR) pathways can modulate cancer risk, progression and therapeutic
      responses. Germline mutations in genes encoding key players in the DNA-damage response (DDR),
      including BRCA1, BRCA2,BLM, FANCA, TP53, RAD51C, and MSH2, result in cancer susceptibility
      syndromes, in part because failure to adequately protect the genome against endogenous and
      exogenous sources of DNA damage results in the accumulation of oncogenic mutations. BRCA1 and
      BRCA2 play a key role in homologous recombination DNA damage repair (HR-DDR) and they are
      considered as the gatekeepers of genomic integrity. Additionally, BRCA interacts with a few
      other DNA repair proteins and forms the complex system for DDR, including ATM, RAD51, PALB2,
      MRE11, RAD50, NBN, PALB2 and the Fanconi anemia proteins genes responsible for the MRN
      complex. PARP inhibitors can be used as an efficient single agent in treatment of tumors
      carrying homologous recombination deficient (HRD), such as germline BRCA mutated or
      HRD-positive ovarian or breast cancers, which exploits the synthetic lethal interaction
      between PARP inhibition and HRdeficiency. Additional clinical data shows olaparib (an oral
      PARP inhibitor) significantly increased activity with responses in mCRPC patients including
      DDR related genes (the BRCA1/2, ATM, PALB2, FANCA and CHK2) mutation. However, the PARP
      inhibitors responses in HR-proficient cancers and platinum-resistant cancers are far more
      modest, and there is apparent drug resistance in most patients with advanced BRCA1/2-mutated
      cancers, as a consequence, these acquired resistances impair sustained antitumor responses of
      PARP inhibitors. Previous data showed that PI3K inhibition led to downregulation of BRCA1 or
      BRCA2 and abrogation of homologous recombination repair (HRR), increased DNA damage, gained
      in poly ADP ribosylation, and then caused the patients were sensitized to PARP inhibitors.
      The mechanistic rationale for the combination of PI3K and PARP inhibitors is that PI3K
      inhibition leads to a downregulation of BRCA1/2 proteins, which increase the degree of HRR
      deficiency inducing a state of Shanghai Haihe Pharmaceutical Co., Ltd Page 18 of 171 Oncology
      Clinical Trial Protocol Protocol No. CYH33-G102 chemical 'BRCAness' in HR-proficient cancers.
      In the absence of competent repair pathways, PARP inhibitors sensitize cells. Importantly,
      synergism between PI3K and PARP inhibitors is observed both in vitro and in HRR-proficient
      and HRR-deficient models of breast cancer animal models. More recently, a phase Ib trial
      provided preliminary clinical evidence of synergism between α-specific PI3K inhibitor
      alpelisib and PARP inhibitor olaparib in epithelial ovarian cancer. Therefore, PARP inhibitor
      and PI3K inhibitor combinations might be applicable to DDR gene mutation and PIK3CA mutation
      advanced solid tumors including ovarian cancers as well as prostate, cervical, endometrial,
      cholangiocarcinoma and breast cancers, also the platinum-resistant ovarian cancer without DDR
      mutations which PARP inhibitor not sufficient activity before. CYH33 is a novel, highly
      potent and selective inhibitor of phosphatidylinositol 3-kinase α (p110α/p85α), significantly
      inhibited the activities of wild-type and mutant PI3Kα kinase as well as the specific mutant
      of E542K, 1047R or E545K, blocked DNA synthesis in G1 phase of cell cycle and suppressed cell
      proliferation, thus exhibited strong activities on inhibiting the growth and proliferation of
      tumors in vitro and in vivo models such as the ovarian and esophageal CDX/PDX models. In dog
      and human hepatocytes, the only metabolite identified was the amide hydrolytic metabolite I27
      On July13, 2018, a Phase I first-in-human dose escalation and expansion single-agent study of
      CYH33 (CYH33-101) started in China (ClinicalTrials.gov identifier: NCT03544905) identifying
      the maximum tolerated dose and assessing safety and preliminary efficacy of singleagent CYH33
      once daily (QD) continuous dosing administration in 28- day cycles. As of December20, 2019,
      20 patients were enrolled and treated at 6 dose levels (1, 5, 10, 20, 40, and 60 mg). For
      pharmacokinetics evaluation of CYH33 monotherapy in advanced solid tumor, study patients,
      over 1-60 mg, were treated with single (1-20 mg) or multiple (1-60 mg with 28 days for a
      cycle) oral daily administration regimen under fast condition. One out of six evaluable
      patients at 40 mg experienced DLT (hyperglycemia), After the cut-off date, 2 out of 5
      evaluable patients at 60mg experienced DLT (hyperglycemia). The MTD of CYH33 single agent was
      determined as 40 mg. For the 20 evaluable patients, the most common adverse events (≥15%) of
      all grades were hyperglycemia (85%), decreased appetite (35%), hypoalbuminemia (30%), blood
      urine present (30%), anemia (30%), diarrhea (25%), nausea (20%), vomiting (20%),
      thrombocytopenia (20%), proteinuria (20%), aspartate aminotransferase (AST) increased (20%),
      and dizziness (20%), weight decreased (15%), rash (15%), pruritus (15%). The most treatment
      related adverse events (≥10%) of all grades were hyperglycemia (85%), decreased appetite
      (25%), diarrhea (20%), nausea (15%), thrombocytopenia (15%), pruritus (15%), rash (10%),
      Shanghai Haihe Pharmaceutical Co., Ltd Page 19 of 171 Oncology Clinical Trial Protocol
      Protocol No. CYH33-G102 weight decreased (10%). The most common treatment related adverse
      events (>5%) of Grade 3 was hyperglycemia. No treatment-related Grade 4 adverse event or
      death was reported in the ongoing trial by the cut-off date. Among 15 patients who had at
      least one post-treatment tumor assessment, partial response (PR) was observed in 2 patients
      at 40 mg, one with colorectal cancer and unknown PIK3CA mutation status, who achieved PR at
      week 12 and confirmed at week 17; the other one with breast cancer harboring PIK3CA mutation
      achieved PR at week 6 and confirmed at week 12. After cut-off date, one additional patient
      with ovarian cancer bearing PIK3CA mutation at 40 mg achieved PR at week 6. PK samples were
      collected in patients enrolled to the CYH33- 101 study. In the interim PK analysis
      (CYH33-101), after oral administration of CYH33 within the dose range of 1-20 mg, the
      absorption of CYH33 was relatively fast (the mean value of Tmax was 1.0 to 4.0 h), and there
      was a slight delay in absorption of the metabolite, I27 (the mean value of Tmax of I27 was
      8.0 to 24.0 h). Within the dose range of studied, the systemic exposure of CYH33 (Cmax,
      AUC0-t, Css, Cmax and AUCss) mostly increased with the increase of dose after single and
      multiple dose administration. The average range of steady state concentration fluctuation
      (DF) was 64.40%~169.49%. Systemic exposure of CYH33+I27 (Css, Cmax and AUCss) was
      approximately proportional to CYH33 dose. Comparing multiple-dose administration (C1D28) with
      first dose administration, before reaching steady state, the exposure of CYH33 + I27
      increased with the increase of time of administration. The steady state was reached by C1D8.
      The purpose of this study is to assess the safety, tolerability and preliminary efficacy of
      CYH33 in combination with olaprib in patients with DDR gene mutations and/or PIK3CA
      mutations, in patients who have progressed on prior PARP inhibitor, and in patients with
      recurrent high grade serous ovarian, fallopian tube, or primary peritoneal cancer who are
      platinum resistant or refractory. The study will assess if this combination will optimize
      anti-tumor activity, block tumor growth and overcome the resistance to PARP inhibitor
      treatment. The study consists 2 parts. In Part 1 dose escalation, the objective is to
      determine the maximum toleration dose (MTD) of the combination. The final recommended phase 2
      dose (RP2D) of CYH33 in combination with olaparib will be based on the totality of an overall
      assessment of available safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD),
      and preliminary efficacy which could be the MTD or a dose level lower in specific cohorts of
      patients. In Part 2 dose expansion, the main objective is to evaluate the efficacy at RP2D.
    

Trial Arms

NameTypeDescriptionInterventions
CYH33 in Combination with OlaparibExperimentalCYH33 in Combination with Olaparib; 20 mg CYH33 QD in combination with olaparib 300 mg BID. Two additional dose levels of CYH33 at 30 mg QD and CYH33 at 40 mg QD in combination with olaparib 300 mg BID will be evaluated.
  • CYH33

Eligibility Criteria

        Inclusion Criteria:

        -

        Patients eligible for inclusion in this study have to meet all of the following criteria:

          1. Provide informed consent voluntarily.

          2. Male and female patients ≥ 18 years of age (or having reached the age of majority
             according to local laws and regulations, if the age is > 18 years).

          3. Patients with advanced solid tumor who have failed at least one line of prior systemic
             therapy or for whom standard therapy do not exist and meet the following eligibility
             for the corresponding part of the study:

               1. Patient must have a histologically or cytologically confirmed diagnosis of
                  advanced recurrent or metastatic solid tumor.

               2. At least one measurable lesion as per RECIST 1.1. (Ovarian cancer participants
                  must have measurable disease by RECIST 1.1 criteria or evaluable cancer via CA125
                  GCIG criteria; Prostate cancer participants must have measurable disease by
                  RECIST 1.1 criteria or evaluable cancer via PSA response).

               3. Population eligibility:

                  • Patients eligible for Part 1 dose escalation: Advanced solid tumors with any
                  DDR gene 1) or PIK3CA 2) mutation who have failed or cannot tolerate standard
                  treatment or currently have no standard treatment.

                  Note:

                    1. DDRa panel: BRCA1, BRCA2, ATM, CDK12, CHEK1, CHEK2, BARD1, BRIP1, FANCL,
                       PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD54L.

                    2. PIK3CA hotspot mutation: E545X, H1047X, or E542K. For the gene mutation
                       testing result either tumor tissue samples or circulating free tumor DNA
                       (ctDNA) test can be accppted.

                       • Patients eligible for Part 2 dose expansion:

                       - Cohort 1: Advanced solid tumors with any selected DDR3) gene mutation

                       - Cohort 2: Advanced solid tumors with PIK3CA hotspot mutation (E545X,
                       H1047X, E542K).

                         -  Cohort 3: Advanced high grade serous ovarian, fallopian tube or primary
                            peritoneal cancer patients with acquired PARP inhibitor resistance4)

                         -  Cohort 4: Advanced solid tumors with any selected DDR3) gene mutation
                            with acquired PARP inhibitor resistance4) .

                         -  Cohort 5: Platinum resistant/refractory5) recurrent high grade serous
                            ovarian, fallopian tube, or primary peritoneal cancer.

                       Note:

                    3. DDRb panel: BRCA1, BRCA2, BARD1, BRIP1, FANCL, PALB2, PPP2R2A, RAD51B,
                       RAD51C, RAD51D, RAD54L. For the gene mutation testing result either tumor
                       tissue samples or circulating free tumor DNA (ctDNA) test can be accepted

                    4. Acquired resistance to prior PARP inhibitor (PARPi) is defined meeting the
                       following criteria: - Patients with advanced solid tumor, with progression
                       on PARPi therapy prior trial consent - Patients should have responded to
                       their prior PARPi therapy (radiology evaluation SD>4months, or CR/PR). -
                       Patients must not have received another antitumor therapy between stopping
                       their previous PARPi therapy and initiating therapy on this trial - Patients
                       must be off prior PARPi for at least 3 weeks or 5 half-lives, whichever is
                       shorter." -

                    5. Platinum refractory or resistance is defined meeting the following criteria:

                         -  Platinum refractory is defined as either relapse less than 2 months
                            after the last platinum-based therapy or relapse during platinum
                            therapy.

                         -  Platinum-resistance is defined as relapse within 2 to 6 months after
                            last dose of platinum-based chemotherapy

          4. Availability of tumor tissue sample (either fresh tumor biopsy or archival tumor
             tissue sample) or blood samples.

          5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

          6. Patient must meet the following laboratory values:

               1. Serum total bilirubin ≤ 1.5 × ULN, (≤ 3.0 mg/dL for patients with Gilbert's
                  syndrome);

               2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
                  (≤ 5.0 × ULN for patients with hepatic metastasis);

               3. Serum creatinine < 1.5 x ULN or creatinine clearance (calculated* or measured
                  value)

                  ≥ 50 mL/min

                  *For calculated creatinine clearance (Clcr) value, the eligibility should be
                  determined using the Cockcroft-Gault formula:

                    -  Male Clcr (mL/mim) = body weight (kg) x (140-age) / [72 x creatinine
                       (mg/dL)]

                    -  Female Clcr (mL/min) = male Clcr x 0.85

               4. Calcium (corrected for serum albumin) and magnesium within normal limits or ≤
                  grade 1 according to NCI-CTCAE version 5.0 if judged clinically not significant
                  by the Investigator;

               5. Potassium within normal limits, or corrected with supplements;

               6. Platelets ≥ 100 x 109/L;

               7. Hemoglobin (Hgb) ≥ 10 g/dL;

               8. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L;

               9. International normalized ratio (INR) < 1.5 (or < 3.0 if on anticoagulation);

              10. Fasting plasma glucose (FPG) ≤ 100 mg/dL (6.1 mmol/L) and Glycosylated Hemoglobin
                  (HbA1c) ≤ 5.7% (both criteria have to be met);

              11. Fasting serum amylase ≤ 2 × ULN;

              12. Fasting serum lipase ≤ ULN

        Exclusion Criteria:

          -  Patients eligible for this study must not meet any of the following criteria:

               1. Patient has received any anticancer therapy (including chemotherapy, targeted
                  therapy, hormonal therapy, biotherapy, immunotherapy, or other investigational
                  agents.) within 28 days or 5 times of half-lives (whichever is shorter) prior to
                  the first dose of the study treatment or who have not recovered from the side
                  effect of such therapy.

               2. Patients with contraindication to olaparib treatment or who did not tolerate
                  olaparib previously.

               3. Patients who had prior treatment with PARP inhibitor, PI3Kα inhibitor, AKT
                  inhibitor or mTOR inhibitor (Part 2 dose expansion cohort 1& 2 only).

               4. Radical radiation therapy (including radiation therapy for over 25% bone marrow)
                  within 4 weeks prior to the first dose of the investigational product or received
                  local palliative radiation therapy for bone metastases within 2 weeks.

               5. Any toxicities from prior treatment that have not recovered to baseline or ≤
                  CTCAE Grade 1 before the start of study treatment, with exception of hair loss.

               6. Patients who have been treated with any hematopoietic colony-stimulating growth
                  factors (e.g., G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug.
                  Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to
                  enrollment, may be continued (Part 1 dose escalation only).

               7. Patients who have symptomatic CNS metastasis which is neurologically unstable or
                  those who have CNS disease requiring increase in the dose of steroid. (Note:
                  Patients withcontrolled CNS metastasis can participate in the trial. Before
                  entering the study, patientsshould have finished radiotherapy, or have received
                  operation for CNS tumor metastasis at least two weeks before. Patients'
                  neurological function must be in a stable state; no newneurological deficit is
                  found during clinical examination and no new problem is found during CNS imaging
                  examinations. If patients need to use steroids to treat CNS metastasis, the
                  therapeutic dose of steroid should be stable for ≥ 3 months at least two weeks
                  prior to entering the study with treatment dose no more than dexamethasone 4 mg
                  daily or anequivalent dose of steroids).

               8. Patients with an established diagnosis of diabetes mellitus including
                  steroid-induced diabetes mellitus.

               9. Major surgery or had significant traumatic injury within 28 days prior to the
                  first dose of the investigational product or has not recovered from major side
                  effects.

              10. Known HIV infection with a history of acquired immunodeficiency syndrome (AIDS)-
                  defining opportunity infection within the past 12 months; active hepatitis B and
                  hepatitis

                  C. Patients whose test results meet one of the following will not be enrolled:

                    -  For patients in China, confirmed HIV antibody positive. For patients in the
                       US, patients with a history of HIV but no history of AIDS or an
                       AIDS-defining opportunistic infection are allowed to be enrolled;

                    -  Serum HBsAg positive and HBV DNA>200 IU/ml or 1000 copies/mL;

                    -  Serum HCV antibody and HCV RNA positive.

              11. Patient has any other concurrent disease which had potential risk of insulin
                  resistance (e.g., pancreatic disorders, acromegaly, Cushing's syndrome) or
                  current use of medication with potential risk of insulin resistance.

              12. Patient with pancreatic cancer.

              13. Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks
                  prior to starting study treatment, or who have not fully recovered from side
                  effects of such treatment.

                  Note: The following uses of corticosteroids are permitted: single doses, topical
                  applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways
                  diseases), eye drops or local injections (e.g., intra-articular).

              14. Use of therapeutic doses of warfarin sodium (Coumadin®), or any other
                  coumarinderivative anticoagulants. The administration of low-molecular weight
                  heparin is allowed.

              15. History of acute pancreatitis within 1 year of screening or past medical history
                  of chronic pancreatitis.

              16. Gastrointestinal condition which could impair absorption of study medication
                  (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea,
                  malabsorption syndrome, or small bowel resection).

              17. Patients with clinically significant cardiovascular disease, including:

                    -  NYHA Class III or higher congestive heart failure;

                    -  History or current evidence of serious uncontrolled ventricular arrhythmias
                       requiring drug therapy;

                    -  Acute myocardial infarction, severe or unstable angina pectoris, coronary
                       artery or peripheral artery bypass graft received within 6 months prior to
                       the first dose;

                    -  Left ventricular ejection fraction (LVEF) < 50%;

                    -  Fridericia's corrected QT interval (QTcF) > 460 ms on ECG conducted during
                       screening;

                    -  Congenital long QT syndrome, or any known history of torsade de pointes
                       (TdP), or family history of unexplained sudden death;

                    -  Clinically uncontrolled hypertension (after standard antihypertensive
                       treatment, systolic blood pressure ≥ 140 mmHg and/or diastolic blood
                       pressure ≥ 90 mmHg).

              18. Any diseases or medical conditions, at the Investigator's discretion, that may be
                  unstable or influence their safety or study compliance, including organ
                  transplantation, abuse of psychotropic medication, alcohol abuse or history of
                  drug abuse.

              19. Other serious illness or medical conditions at the Investigator's discretion,
                  that may influence study results, including but not limited to serious infection,
                  diabetes, cardiovascular and cerebrovascular diseases or lung disease.

              20. Participation in a prior investigational treatment within 28 days prior to the
                  start of study treatment or within 5 half-lives of the investigational product
                  (whichever is no longer than 28 days).

              21. Pregnant or breast-feeding patients. Pregnancy refers to the state of a woman
                  between fertilization and the end of pregnancy confirmed by positive laboratory
                  hCG test (> 5 mIU/mL). Breast-feeding woman can become eligible for this study if
                  she stops breastfeeding, however, cannot restart the breast-feeding on/after the
                  completion of the study treatment.

              22. Male and female of childbearing potential not using effective contraception (e.g.

        intrauterine device (IUD), diaphragm with spermicide, cervical cap with spermicide, male
        condoms, female condoms with spermicide, oral hormonal contraceptive) during the trial and
        within 6 months after the end of treatment. Definition of child-bearing potential: a female
        that fulfills the one of the following criteria is considered to be without childbearing
        potential: spontaneous menopause for 12 consecutive months with appropriate clinical
        features (e.g. proper age, a history of vasomotor diseases, etc.), or a history of
        bilateral ovariectomy (with or without hysterectomy) or tubal ligation performed at least 6
        weeks. For patients with amenorrhea due to anti-tumor agents, even amenorrhea over 12
        months, a pregnancy test is necessary. If a female only received an ovariectomy, she will
        be considered as no childbearing potential only after confirmation by hormone levels.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicities (DLT)
Time Frame:12 months
Safety Issue:
Description:Incidence rate of dose limiting toxicities (DLT) in the first cycle (of 28 days) of each investigated dose levels.

Secondary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame:38 months
Safety Issue:
Description:Number, type, incidence, duration, severity and seriousness of adverse events (AEs) as assessed by CTCAE v5.0
Measure:Disease control rate (DCR)
Time Frame:38 months
Safety Issue:
Description:Disease control rate (DCR) defined as the sum of CR, PR and stable disease (SD) by RECIST version 1.1. - Progression Free Survival (PFS).
Measure:Pharmacokinetic measures - Plasma concentration time Area Under the Curve
Time Frame:12 months
Safety Issue:
Description:Measure the variation of CHY33/olaparib concentration in blood plasma as a function of time
Measure:Pharmacokinetic measures - Cmax
Time Frame:12 months
Safety Issue:
Description:Measure the maximum (peak) plasma concentration(s) of CHY33/olaparib
Measure:Pharmacokinetic measures - Tmax
Time Frame:12 months
Safety Issue:
Description:Measure of time to reach maximum (peak) plasma concentration(s) following administration of CHY33/olaparib
Measure:Pharmacokinetic measures - CL/F
Time Frame:12 months
Safety Issue:
Description:Measure apparent total clearance(s) of CHY33/olaparib from plasma after oral administration
Measure:Pharmacokinetic measures - Vz/F
Time Frame:12 months
Safety Issue:
Description:Measure apparent volume of distribution during terminal phase after administration of CHY33/olaparib
Measure:Pharmacokinetic measures - terminal half- life (t1/2)
Time Frame:12 months
Safety Issue:
Description:Measure elimination half-life of CHY33/olaparib, when administered in combination

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ShangHai HaiHe Pharmaceutical

Last Updated

October 7, 2020