Informations générales (source: ClinicalTrials.gov)
A Single-Arm, Open-Label, Multicenter Phase 2 Study to Evaluate the Efficacy and Safety of Taletrectinib in Patients With Advanced or Metastatic ROS1 Positive NSCLC and Other Solid Tumors
Interventional
Phase 2
Nuvation Bio Inc. (Voir sur ClinicalTrials)
septembre 2021
décembre 2027
02 novembre 2025
The main purpose of the study is to evaluate safety and efficacy of taletrectinib (also
known as AB-106 or DS-6051b) monotherapy in the treatment of advanced NSCLC.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Benjamin BESSE | 21/06/2024 15:51:36 | Contacter | ||
Critères
Tous
Inclusion Criteria:
1. Age ≥18 years (or ≥20 years as required by local regulations).
2. Histologically or cytologically confirmed diagnosis of locally advanced (including
inoperable Stage IIIA or IIIB NSCLC) or metastatic NSCLC (Cohorts 1-3, 5) or other
solid tumors including NSCLC patients ineligible for other cohorts (Cohort 4).
3. Evidence of ROS1 fusion by a validated assay as performed in Clinical Laboratory
Improvement Amendments (CLIA)-certified or locally equivalent diagnostic
laboratories. The molecular assays (i.e., Reverse Transcription Polymerase Chain
Reaction [RT-PCR], Next-generation Sequencing [NGS]) are highly recommended.
4. Sufficient tumor tissue is required for patients in Cohort 1 and for TKI-naïve
patients in Cohort 5 in order to perform confirmatory ROS1 fusion testing at the
designated central laboratories. For patients in Cohort 1 and for TKI-naïve patients
in Cohort 5, an archival tumor tissue specimen should be available and collected
prior to enrollment. If archival tumor tissue is unavailable, then a fresh biopsy
must be performed. Tumor tissue for patients in other cohorts is highly recommended,
and tumor tissue obtained after progression on the most recent prior ROS1 TKI
therapy in these cohorts is preferred. Cytology samples (e.g., pleural effusion cell
pellets) may be acceptable for patients in Cohorts 2-4, and patients in Cohort 5
that received prior treatment with TKI(s) having ROS1 activity.
5. Patients with central nervous system (CNS) involvement, including leptomeningeal
carcinomatosis, must be stable (either asymptomatic or previously treated and
controlled are allowed:
- Seizure prophylaxis is permitted with non-enzyme inducing anti-epileptic drugs
(non-EIAEDs).
- Corticosteroid treatment at a stable or decreasing dose within 7 days prior to
the first dose of taletrectinib.
- Whole brain radiation therapy (WBRT) must be completed at least 14 days
and stereotactic radiotherapy, stereotactic radiosurgery, or gamma knife
radiotherapy at least 7 days prior to enrollment; the patient must be
clinically stable for 7 days according to investigator judgement prior to
first dose of taletrectinib.
6. The patient can be either ROS1 TKI treatment naïve or treated with prior ROS1
TKI(s):
o Cohort 1: Patients with locally advanced or metastatic ROS1-positive NSCLC.
Systemic chemotherapy naïve or pretreated with 1 prior line of chemotherapy but
never treated with any ROS1 TKI.
o Cohort 2: Patients with locally advanced or metastatic ROS1-positive NSCLC. Prior
treatment with 1 approved ROS1 TKI (crizotinib or entrectinib) and disease
progression. The patient can be either chemotherapy naïve or has received 1 line of
systemic chemotherapy for locally advanced or metastatic ROS1-positive NSCLC.
- Cohort 3: Patients with locally advanced or metastatic ROS1-positive NSCLC.
Prior treatment with ≥2 TKIs with ROS1 activity and disease progression. The
patient can be either chemotherapy naïve or has received 1 line of systemic
chemotherapy for locally advanced or metastatic ROS1-positive NSCLC, patients
with known ROS1 resistant mutations are preferred.
- Cohort 4: Patients with other ROS1-positive solid tumors, or NSCLC patients
ineligible for Cohorts 1-3. Prior treatment with ≤3 TKIs with ROS1 activity.
The patient can be either chemotherapy naïve or has received ≤2 lines of
systemic chemotherapy for locally advanced or metastatic solid tumors.
- Cohort 5: Patients with locally advanced or metastatic ROS1-positive NSCLC. The
patient can be either chemotherapy naïve or has received ≤2 lines of systemic
chemotherapy line of systemic chemotherapy for locally advanced or metastatic
ROS1-positive NSCLC. ROS1-TKI-naïve or pretreated with TKI(s) having ROS1
activity.
7. At least 1 measurable disease per RECIST 1.1 as assessed by the investigator.
8. Eastern Cooperative Oncology Group Performance Status: 0 or 1.
9. Patient with a life expectancy ≥12 weeks based on the judgement of investigator.
10. Patients with adequate organ function meeting the following criteria:
1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤3.0 ×
upper limit of normal (ULN) (or ≤5.0 × ULN, for patients with concurrent liver
metastases)
2. Serum total bilirubin: ≤1.5 × ULN (≤3.0 × ULN for patients with Gilbert
syndrome or if liver function abnormalities are due to underlying malignancy)
3. Absolute neutrophil count: ≥1,500/μL
4. Platelet count: ≥100,000/μL
5. Hemoglobin: ≥9.0 g/dL
6. Serum creatinine ≤1.5 × ULN and estimated creatinine clearance (CLcr) ≥45
mL/min as calculated using the method standard for the institution (e.g.,
Cockcroft - Gault Equation)
11. Males and/or females who meet any of the following criteria:
a. For males (irrespective of surgical sterilization [vasectomy]): agree to use
effective contraception methods during the study intervention period and for at
least 90 days after the last dose of investigational drug or agree with complete
abstinence.
b. Females without menses for at least 1 year prior to screening or documented to be
surgically sterilized. Women of childbearing potential (WOCBP) must agree to use two
concurrent highly effective methods of contraception or agree with complete
abstinence from sexual intercourse since the informed consent until 45 days after
the last dose of investigational drug. Usage of hormonotherapy for contraception
should be recorded as well.
12. For all females of childbearing potential, a negative pregnancy test must be
obtained within 7 days before starting study treatment. Female patients of non
childbearing potential must meet at least 1 of the following criteria:
○ Achieved postmenopausal status, defined as follows: cessation of regular menses
for at least 12 consecutive months with no alternative pathological or physiological
cause; status may be confirmed with a serum follicle stimulating hormone (FSH) level
confirming the postmenopausal state.
○ Have undergone a documented hysterectomy and/or bilateral oophorectomy.
○ Have medically confirmed ovarian failure. All other female patients (including
female patients with tubal ligations) are considered to be of childbearing
potential.
13. The patient is willing and capable to give written informed consent.
14. The patient is willing and capable to comply with the study scheduled visits,
treatment plans, laboratory tests and other procedures.
15. The patient is willing and capable to comply with study site's COVID-19 policies.
Exclusion Criteria
1. Treatment with small molecule anticancer therapy including other investigational
agents or cytotoxic systemic anticancer therapy within 2 weeks (or 5 half-lives of
the compound, whichever is shorter) prior to the first dose of taletrectinib; or
treatment with monoclonal antibodies, including immune checkpoint inhibitors within
4 weeks before the first dose of taletrectinib.
2. Major surgical procedure, open biopsy, or significant traumatic injury ≤4 weeks
before the first dose of taletrectinib.
Note: Placement of vascular access device is not considered major surgery. Other
minor surgical procedures, such as catheter placement or minimally invasive biopsy,
are allowed.
3. Radiation outside the chest and brain <7 days prior to C1D1.
4. Have been diagnosed with another primary malignancy other than NSCLC except for
adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively
treated non-metastatic prostate cancer; or patients with another primary malignancy
who are definitively relapse-free with at least 3 years elapsed since the diagnosis
of the other primary malignancy.
5. Adverse events due to prior therapy are unresolved to ≤ CTCAE Grade 1 or has not
returned to baseline, by the first dose of taletrectinib except for AEs not
constituting a safety risk to the patient based on the judgment of investigators.
6. Patients with untreated spinal cord compression caused by tumor and/or cancerous
meningitis.
7. History or evidence of interstitial fibrosis, interstitial lung disease or
drug-induced pneumonitis (Excluding clinically insignificant or asymptomatic post
radiation pneumonitis).
8. Any gastrointestinal disorders that may affect absorption of oral medications.
1. 9. Active and clinically significant bacterial, fungal, or viral infection including
hepatitis B virus (HBV), hepatitis C virus (HCV), or severe acute respiratory syndrome
coronavirus 2 (SARS CoV 2), known human immunodeficiency virus (HIV) or acquired
immunodeficiency syndrome (AIDS) related illness. Note that the following are permitted:
○ Patients treated for hepatitis C (HCV) or HIV with no detectable viral load; for at
least 1 month prior to the first dose of taletrectinib.
Note: caution with drug drug interactions of concomitant anti HIV agents and CYP3A
substrates.
○ Patients with known hepatitis B (HBV) infections:
- With past or resolved HBV infection (defined as the presence of hepatitis B core
antibody [HBcAb] and absence of hepatitis B surface antigen [HBsAg]); or
- With inactive HBV carrier state (defined as HBsAg positive, with normal ALT, and HBV
DNA <2,000 IU/mL or <10,000 copies/mL).
Note: Please consider that, for patients in an inactive HBV carrier state or with a
resolved HBV infection, there may be a risk of HBV reactivation, and anti HBV prophylaxis
should be considered.
10. Clinically significant cardiovascular diseases within 3 months prior to the first
dose of taletrectinib: myocardial infarction, severe/unstable angina, coronary/peripheral
endovascular treatment, heart failure or cerebrovascular disorder including transient
ischemic attack.
11. Ongoing cardiac dysrhythmias of ≥ CTCAE Grade 2, uncontrolled atrial fibrillation of
any grade, or QT interval corrected for heart rate by Fredericia's formula (QTcF) >470
milliseconds, or symptomatic bradycardia <45 beats per minute; patient has family or
medical history of long QT syndrome.
12. Pregnancy or lactation/breastfeeding. 13. Use of food or drugs that are known potent
cytochrome P450 3A4/5 (CYP3A4/5) inhibitors or inducers or P-glycoprotein inhibitors or
inducers within 14 days prior to the first dose of study treatment and while on
treatment.
14. Administration of agents with potential QT interval prolonging effect within 14 days
prior to first dose of study treatment and while on treatment.
15. Patients with other severe medical or mental diseases in whom the risk is increased
by participation to the study or treatment with study treatment in the opinion of the
investigator.
1. Age ≥18 years (or ≥20 years as required by local regulations).
2. Histologically or cytologically confirmed diagnosis of locally advanced (including
inoperable Stage IIIA or IIIB NSCLC) or metastatic NSCLC (Cohorts 1-3, 5) or other
solid tumors including NSCLC patients ineligible for other cohorts (Cohort 4).
3. Evidence of ROS1 fusion by a validated assay as performed in Clinical Laboratory
Improvement Amendments (CLIA)-certified or locally equivalent diagnostic
laboratories. The molecular assays (i.e., Reverse Transcription Polymerase Chain
Reaction [RT-PCR], Next-generation Sequencing [NGS]) are highly recommended.
4. Sufficient tumor tissue is required for patients in Cohort 1 and for TKI-naïve
patients in Cohort 5 in order to perform confirmatory ROS1 fusion testing at the
designated central laboratories. For patients in Cohort 1 and for TKI-naïve patients
in Cohort 5, an archival tumor tissue specimen should be available and collected
prior to enrollment. If archival tumor tissue is unavailable, then a fresh biopsy
must be performed. Tumor tissue for patients in other cohorts is highly recommended,
and tumor tissue obtained after progression on the most recent prior ROS1 TKI
therapy in these cohorts is preferred. Cytology samples (e.g., pleural effusion cell
pellets) may be acceptable for patients in Cohorts 2-4, and patients in Cohort 5
that received prior treatment with TKI(s) having ROS1 activity.
5. Patients with central nervous system (CNS) involvement, including leptomeningeal
carcinomatosis, must be stable (either asymptomatic or previously treated and
controlled are allowed:
- Seizure prophylaxis is permitted with non-enzyme inducing anti-epileptic drugs
(non-EIAEDs).
- Corticosteroid treatment at a stable or decreasing dose within 7 days prior to
the first dose of taletrectinib.
- Whole brain radiation therapy (WBRT) must be completed at least 14 days
and stereotactic radiotherapy, stereotactic radiosurgery, or gamma knife
radiotherapy at least 7 days prior to enrollment; the patient must be
clinically stable for 7 days according to investigator judgement prior to
first dose of taletrectinib.
6. The patient can be either ROS1 TKI treatment naïve or treated with prior ROS1
TKI(s):
o Cohort 1: Patients with locally advanced or metastatic ROS1-positive NSCLC.
Systemic chemotherapy naïve or pretreated with 1 prior line of chemotherapy but
never treated with any ROS1 TKI.
o Cohort 2: Patients with locally advanced or metastatic ROS1-positive NSCLC. Prior
treatment with 1 approved ROS1 TKI (crizotinib or entrectinib) and disease
progression. The patient can be either chemotherapy naïve or has received 1 line of
systemic chemotherapy for locally advanced or metastatic ROS1-positive NSCLC.
- Cohort 3: Patients with locally advanced or metastatic ROS1-positive NSCLC.
Prior treatment with ≥2 TKIs with ROS1 activity and disease progression. The
patient can be either chemotherapy naïve or has received 1 line of systemic
chemotherapy for locally advanced or metastatic ROS1-positive NSCLC, patients
with known ROS1 resistant mutations are preferred.
- Cohort 4: Patients with other ROS1-positive solid tumors, or NSCLC patients
ineligible for Cohorts 1-3. Prior treatment with ≤3 TKIs with ROS1 activity.
The patient can be either chemotherapy naïve or has received ≤2 lines of
systemic chemotherapy for locally advanced or metastatic solid tumors.
- Cohort 5: Patients with locally advanced or metastatic ROS1-positive NSCLC. The
patient can be either chemotherapy naïve or has received ≤2 lines of systemic
chemotherapy line of systemic chemotherapy for locally advanced or metastatic
ROS1-positive NSCLC. ROS1-TKI-naïve or pretreated with TKI(s) having ROS1
activity.
7. At least 1 measurable disease per RECIST 1.1 as assessed by the investigator.
8. Eastern Cooperative Oncology Group Performance Status: 0 or 1.
9. Patient with a life expectancy ≥12 weeks based on the judgement of investigator.
10. Patients with adequate organ function meeting the following criteria:
1. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤3.0 ×
upper limit of normal (ULN) (or ≤5.0 × ULN, for patients with concurrent liver
metastases)
2. Serum total bilirubin: ≤1.5 × ULN (≤3.0 × ULN for patients with Gilbert
syndrome or if liver function abnormalities are due to underlying malignancy)
3. Absolute neutrophil count: ≥1,500/μL
4. Platelet count: ≥100,000/μL
5. Hemoglobin: ≥9.0 g/dL
6. Serum creatinine ≤1.5 × ULN and estimated creatinine clearance (CLcr) ≥45
mL/min as calculated using the method standard for the institution (e.g.,
Cockcroft - Gault Equation)
11. Males and/or females who meet any of the following criteria:
a. For males (irrespective of surgical sterilization [vasectomy]): agree to use
effective contraception methods during the study intervention period and for at
least 90 days after the last dose of investigational drug or agree with complete
abstinence.
b. Females without menses for at least 1 year prior to screening or documented to be
surgically sterilized. Women of childbearing potential (WOCBP) must agree to use two
concurrent highly effective methods of contraception or agree with complete
abstinence from sexual intercourse since the informed consent until 45 days after
the last dose of investigational drug. Usage of hormonotherapy for contraception
should be recorded as well.
12. For all females of childbearing potential, a negative pregnancy test must be
obtained within 7 days before starting study treatment. Female patients of non
childbearing potential must meet at least 1 of the following criteria:
○ Achieved postmenopausal status, defined as follows: cessation of regular menses
for at least 12 consecutive months with no alternative pathological or physiological
cause; status may be confirmed with a serum follicle stimulating hormone (FSH) level
confirming the postmenopausal state.
○ Have undergone a documented hysterectomy and/or bilateral oophorectomy.
○ Have medically confirmed ovarian failure. All other female patients (including
female patients with tubal ligations) are considered to be of childbearing
potential.
13. The patient is willing and capable to give written informed consent.
14. The patient is willing and capable to comply with the study scheduled visits,
treatment plans, laboratory tests and other procedures.
15. The patient is willing and capable to comply with study site's COVID-19 policies.
Exclusion Criteria
1. Treatment with small molecule anticancer therapy including other investigational
agents or cytotoxic systemic anticancer therapy within 2 weeks (or 5 half-lives of
the compound, whichever is shorter) prior to the first dose of taletrectinib; or
treatment with monoclonal antibodies, including immune checkpoint inhibitors within
4 weeks before the first dose of taletrectinib.
2. Major surgical procedure, open biopsy, or significant traumatic injury ≤4 weeks
before the first dose of taletrectinib.
Note: Placement of vascular access device is not considered major surgery. Other
minor surgical procedures, such as catheter placement or minimally invasive biopsy,
are allowed.
3. Radiation outside the chest and brain <7 days prior to C1D1.
4. Have been diagnosed with another primary malignancy other than NSCLC except for
adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively
treated non-metastatic prostate cancer; or patients with another primary malignancy
who are definitively relapse-free with at least 3 years elapsed since the diagnosis
of the other primary malignancy.
5. Adverse events due to prior therapy are unresolved to ≤ CTCAE Grade 1 or has not
returned to baseline, by the first dose of taletrectinib except for AEs not
constituting a safety risk to the patient based on the judgment of investigators.
6. Patients with untreated spinal cord compression caused by tumor and/or cancerous
meningitis.
7. History or evidence of interstitial fibrosis, interstitial lung disease or
drug-induced pneumonitis (Excluding clinically insignificant or asymptomatic post
radiation pneumonitis).
8. Any gastrointestinal disorders that may affect absorption of oral medications.
1. 9. Active and clinically significant bacterial, fungal, or viral infection including
hepatitis B virus (HBV), hepatitis C virus (HCV), or severe acute respiratory syndrome
coronavirus 2 (SARS CoV 2), known human immunodeficiency virus (HIV) or acquired
immunodeficiency syndrome (AIDS) related illness. Note that the following are permitted:
○ Patients treated for hepatitis C (HCV) or HIV with no detectable viral load; for at
least 1 month prior to the first dose of taletrectinib.
Note: caution with drug drug interactions of concomitant anti HIV agents and CYP3A
substrates.
○ Patients with known hepatitis B (HBV) infections:
- With past or resolved HBV infection (defined as the presence of hepatitis B core
antibody [HBcAb] and absence of hepatitis B surface antigen [HBsAg]); or
- With inactive HBV carrier state (defined as HBsAg positive, with normal ALT, and HBV
DNA <2,000 IU/mL or <10,000 copies/mL).
Note: Please consider that, for patients in an inactive HBV carrier state or with a
resolved HBV infection, there may be a risk of HBV reactivation, and anti HBV prophylaxis
should be considered.
10. Clinically significant cardiovascular diseases within 3 months prior to the first
dose of taletrectinib: myocardial infarction, severe/unstable angina, coronary/peripheral
endovascular treatment, heart failure or cerebrovascular disorder including transient
ischemic attack.
11. Ongoing cardiac dysrhythmias of ≥ CTCAE Grade 2, uncontrolled atrial fibrillation of
any grade, or QT interval corrected for heart rate by Fredericia's formula (QTcF) >470
milliseconds, or symptomatic bradycardia <45 beats per minute; patient has family or
medical history of long QT syndrome.
12. Pregnancy or lactation/breastfeeding. 13. Use of food or drugs that are known potent
cytochrome P450 3A4/5 (CYP3A4/5) inhibitors or inducers or P-glycoprotein inhibitors or
inducers within 14 days prior to the first dose of study treatment and while on
treatment.
14. Administration of agents with potential QT interval prolonging effect within 14 days
prior to first dose of study treatment and while on treatment.
15. Patients with other severe medical or mental diseases in whom the risk is increased
by participation to the study or treatment with study treatment in the opinion of the
investigator.