IIIb/IV NSCLC With T790M Positive Mutations Failed to Osimertinib TherapyPhase 2NCT04316351

Efficacy and Safety of Toripalimab (JS001) Combined With Pemetrexed and Anlotinib for Patients With T790M Positive Non-Small Cell Lung Cancer After Osimertinib Resistance

A Phase 2 study testing Toripalimab + Pemetrexed + Anlotinib in people with IIIb/IV NSCLC With T790M Positive Mutations Failed to Osimertinib Therapy, run by Guangzhou Institute of Respiratory Disease at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

This is an open-label, single-arm, multi-center, phase II exploratory study that evaluates the efficacy and safety of Toripalimab injection (JS001) combined with Pemetrexed and Anlotinib as a second-line treatment for patients with T790M positive Non-Small Cell Lung Cancer (IIIb / IV ) after Osimertinib resistance. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: IIIb/IV NSCLC With T790M Positive Mutations Failed to Osimertinib Therapy
What is being tested?: Toripalimab + Pemetrexed + Anlotinib
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 60 participants
Where: 1 siteChina
Study dates: 1 Apr 2020to 1 Apr 2022
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Fully understand this study and voluntarily sign the informed consent form (ICF);
Histologically and/or cytologically confirmed Stage IIIb / IV NSCLC (according to the seventh edition of AJCC); patients with T790M-positive mutations who were resistant to Osimertinib treatment;
At least one measurable lesion (according to RECIST 1.1); Note: Lesions that have previously received radiotherapy cannot be regarded as target lesions, unless the lesions clearly progress after radiotherapy;
Agree to provide formalin-fixed tumor specimens or biopsy specimens after the subject is diagnosed with metastatic cancer, at least 15 sections; if the recent biopsy is not feasible, allow to receive biopsy specimens before adjuvant/neo-adjuvant chemotherapy (archived specimens);
ECOG PS 0-2
Life expectancy ≥3 months.

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The laboratory examination results within 7 days before enrollment must meet the following standards:
Neutrophils ≥1.5 × 109 / L;
Platelets ≥100 × 109 / L;
Hemoglobin ≥90g / L (no infusion of concentrated red blood cells within 4 weeks);
Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 50 mL / min;
Total serum bilirubin ≤ 1.5 × ULN;
AST and ALT ≤ 2.5 × ULN; in patients with liver metastases, ALT and AST ≤ 5 × ULN;
International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN unless the subject is receiving anticoagulant therapy; Activated partial thrombin time (aPTT) or partial thrombin time (PTT) ≤ 1.5 × ULN unless the subject is receiving anticoagulant therapy.
Women of childbearing age must confirm that the serum pregnancy test is negative and agree to use effective contraception during drug use and within 60 days after the last dose. Women of childbearing age are defined as sexually mature women in this program: 1) not undergoing hysterectomy or bilateral ovariectomy, 2) natural menopause has not continued for 12 months (amenorrhea after cancer treatment does not exclude fertility).

Who cannot join

Incorporate other driver gene mutations with known drug treatments, including but not limited to: ALK gene rearrangement, ROS1 mutation, BRAF600E mutation, etc .;
Received systemic chemotherapy for advanced NSCLC within 4 weeks before enrollment;
Have received EGFR-TKI treatment within 2 weeks before enrollment;
Received radiotherapy within 4 weeks or radiopharmaceutical treatment within 8 weeks before enrollment, except for local palliative radiotherapy for bone metastases;
Uncontrollable or symptomatic hypercalcemia (> 1.5mmol / L ionized calcium or calcium> 12 mg / dL or corrected serum calcium> ULN);
Have undergone major surgery or have not completely recovered from the previous operation within 4 weeks before enrollment ;

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The toxicity of previous antitumor treatment has not recovered to CTCAE 0-1, except for hair loss；
Active or untreated CNS metastases detected by CT or MRI before screening and imaging evaluation: If a new asymptomatic CNS metastases is detected during the screening period , it must undergo radiation therapy and / or surgery . After treatment, if met all other criteria, no additional brain scan is required . Patients who have previously received brain or meningeal metastasis treatment and maintained clinical stability for at least 2 weeks, stopped systemic hormonal therapy (> 10 mg / day of prednisone or other equivalent hormones) for more than 2 weeks can be included;
Spinal cord compression that has not undergone radical surgery and / or radiation therapy, or previously diagnosed spinal cord compression with no clinical evidence showing that the disease is stable for ≥ 4 weeks before enrollment
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once a month or more frequently);
have a history of idiopathic pulmonary fibrosis, organizing pneumonia (such as occlusive bronchiolitis), drug-induced pneumonia, idiopathic pneumonia, or have evidence of active pneumonia detected by chest CT;
Clinically uncontrolled active infections, including but not limited to acute pneumonia;
Past or present with other malignancies (except for non-melanoma skin basal cell carcinoma, breast / cervical carcinoma in situ, and other malignancies that have not been treated in the past five years and have been effectively controlled);
The patients have any active autoimmune disease or a history of autoimmune disease (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, nephritis, hyperthyroidism, reduced thyroid function; Patients with vitiligo or childhood asthma that have completely recovered and do not require any intervention in adults can be included; asthma with bronchodilators required for medical intervention cannot be included);
Known clinically significant liver diseases, including active viral hepatitis, alcoholic hepatitis or other hepatitis, cirrhosis, fatty liver, hereditary liver disease, uncontrollable major seizures, or superior vena cava syndrome;
Previously used anti-PD-1 antibody, anti-PD-L1 antibody or anti-CTLA-4 antibody (or any other antibody acting on T cell co-stimulation or checkpoint pathway).
Patients with active tuberculosis (TB) are receiving antituberculosis treatment or have received antituberculosis treatment within 1 year before screening;
After obtaining the approval of the clinical monitor, patients within 4 weeks before the first medication patients receiving systemic immunosuppressive drugs (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and TNF-α ) or receiving short-term, low-dose systemic immunosuppressive drugs or receiving one-time shock therapy with systemic immunosuppressive drugs (eg, 48 hours of glucocorticoid treatment for contrast allergic reactions) can be enrolled in the study. Patients receiving mineralocorticoids (such as fludrocortisone), corticosteroids for chronic obstructive pulmonary disease or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible to participate in the study;
Have received any anti-infective vaccine (such as influenza vaccine, chickenpox vaccine, etc.) within 4 weeks before enrollment;
A pregnant or lactating woman or a woman who may be pregnant have a positive pregnancy test before the first use of the drug; a patient with fertility who is unwilling to receive contraceptives or her sexual partner is unwilling to receive contraceptives;
History of HIV infection
Patients who had obvious hemoptysis (>50ml/day) within 3 months before enrollment; Patients who experienced bleeding symptoms of clinical significance or with confirmed bleeding tendency such as hemorrhage of digestive tract, hemorrhagic gastric ulcer, baseline occult blood in stool ++ and above, or vasculitis, etc within 3 months before enrollment ;
Any other disease or condition of clinical significance that the investigator believes may affect protocol compliance, or affect the signing of an ICF, or is not suitable for participation in this clinical trial;
A history of severe allergies, allergies or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins;
Patients who are allergic to known biological drugs produced by Chinese hamster ovary cells, or citric acid monohydrate, sodium citrate dihydrate, mannitol, polysorbate (a component of the test drug);
Patients who have previously received an allogeneic stem cell or parenchymal organ transplant.
CT or MRI shows that tumor locate within a distance of less than 5 mm from the large vessels, or there is a central tumor that invades the local large blood vessels; or there are obvious pulmonary cavity or necrotic tumors;
Patients who manifested arterial/venous thrombus events, e.g. cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep venous thrombosis and pulmonary embolism, etc., within 12 months before screening.

Trial locations and contacts

1 site in 1 country.

zhou cheng zhi, Doctor contact

(+86)13560351186

doctorzcz@163.com

China1 site, 1 recruiting

Zhou Chengzhi
Guangzhou, Guangdong, 510120
Chengzhi Zhou, Professor, 13560351186, doctorzcz@163.com
Recruiting

Other trials in China

About this study

Official title: Efficacy and Safety of Toripalimab (JS001) Combined With Pemetrexed and Anlotinib for Patients With T790M Positive Non-Small Cell Lung Cancer After Osimertinib Resistance：a Phase II,Muti-center, Single Arm Study

Conditions: IIIb/IV NSCLC With T790M Positive Mutations Failed to Osimertinib Therapy
Being tested: Toripalimab + Pemetrexed + Anlotinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Toripalimab + Pemetrexed + AnlotinibDrug
Also called JS001
Toripalimab 240 mg iv d1 + anlotinib 12mg po d1-d14 + pemetrexed 500mg / m2 d1 Q3W for 4 cycles, followed by Toripalimab 240mg iv d1 + anlotinib 12mg po d1 + pemetrexed 500mg / m2 d1 Q3W for another 31 cycles (up to a total of 35 cycles).
If there is no disease progression, patients will receive anlotinib po 12mg d1-d14 + pemetrexed 500mg / m2 d1, Q3W for maintenance therapy until PD per RECIST v1.1 or loss of clinical benefit.

Study groups in NCT04316351
Study group	Role	What they receive
Toripalimab + Pemetrexed + Anlotinib	Experimental	Not described Receives: Drug: Toripalimab + Pemetrexed + Anlotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall response rate （ORR）
Defined as percentage of participants achieving complete response (CR) and partial response (PR) assessed by the Independent Review Committee (IRC) according to the RECIST 1.1
Measured: two years

Secondary outcomes (5)

Progression-free survival (PFS)
assessed by IRC and researchers based on RECIST 1.1
Measured: two years
Overall survival (OS)
assessed by IRC and researchers based on RECIST 1.1
Measured: two years
Disease Control Rate (DCR)
assessed by IRC and researchers based on RECIST 1.1
Measured: two years
Duration of disease response (DOR)
assessed by IRC and researchers based on RECIST 1.1
Measured: two years
overall incidence of adverse events (AE)
overall incidence of adverse events (AE); incidence of grade 3 or higher AE; incidence of severe adverse events (SAE); incidence of AEs leading to discontinuation of drug use; incidence of AEs leading to suspension of drug use.
Measured: two years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Apr 20201 Apr 2022

First posted20 Mar 2020
Study start1 Apr 2020
Primary completion1 Apr 2022 (estimated)
Study completion1 Apr 2022 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for IIIb/IV NSCLC With T790M Positive Mutations Failed to Osimertinib TherapyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 60 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04316351
Sponsor's protocol ID: CROC2002
Status last verified: Jul 2020
First submitted: 19 Mar 2020
Last updated: 23 Jul 2020
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 23 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Efficacy and Safety of Toripalimab (JS001) Combined With Pemetrexed and Anlotinib for Patients With T790M Positive Non-Small Cell Lung Cancer After Osimertinib Resistance：a Phase II,Muti-center, Single Arm Study
ClinicalTrials.gov ID: NCT04316351
Acronym / sponsor ID: CROC2002
Conditions: IIIb/IV NSCLC With T790M Positive Mutations Failed to Osimertinib Therapy
Phase: Phase 2
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 60 participants (estimated)
Lead sponsor: Guangzhou Institute of Respiratory DiseaseUniversity, hospital or other
Collaborators: Shanghai Junshi Bioscience Co., Ltd.
Study start: 1 Apr 2020 (actual)
Primary completion: 1 Apr 2022 (estimated)
Study completion: 1 Apr 2022 (estimated)
First posted: 20 Mar 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Toripalimab + Pemetrexed + Anlotinib	Experimental	Drug: Toripalimab + Pemetrexed + Anlotinib

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (15 listed)

Fully understand this study and voluntarily sign the informed consent form (ICF);
Histologically and/or cytologically confirmed Stage IIIb / IV NSCLC (according to the seventh edition of AJCC); patients with T790M-positive mutations who were resistant to Osimertinib treatment;
At least one measurable lesion (according to RECIST 1.1); Note: Lesions that have previously received radiotherapy cannot be regarded as target lesions, unless the lesions clearly progress after radiotherapy;
Agree to provide formalin-fixed tumor specimens or biopsy specimens after the subject is diagnosed with metastatic cancer, at least 15 sections; if the recent biopsy is not feasible, allow to receive biopsy specimens before adjuvant/neo-adjuvant chemotherapy (archived specimens);
ECOG PS 0-2

Key exclusion criteria (28 listed)

Incorporate other driver gene mutations with known drug treatments, including but not limited to: ALK gene rearrangement, ROS1 mutation, BRAF600E mutation, etc .;
Received systemic chemotherapy for advanced NSCLC within 4 weeks before enrollment;
Have received EGFR-TKI treatment within 2 weeks before enrollment;
Received radiotherapy within 4 weeks or radiopharmaceutical treatment within 8 weeks before enrollment, except for local palliative radiotherapy for bone metastases;
Uncontrollable or symptomatic hypercalcemia (> 1.5mmol / L ionized calcium or calcium> 12 mg / dL or corrected serum calcium> ULN);

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Toripalimab + Pemetrexed + AnlotinibAlso: JS001Toripalimab 240 mg iv d1 + anlotinib 12mg po d1-d14 + pemetrexed 500mg / m2 d1 Q3W for 4 cycles, followed by Toripalimab 240mg iv d1 + anlotinib 12mg po d1 + pemetrexed 500mg / m2 d1 Q3W for another 31 cycles (up to a total of 35 cycles). If there is no disease progression, patients will receive anlotinib po 12mg d1-d14 + pemetrexed 500mg / m2 d1, Q3W for maintenance therapy until PD per RECIST v1.1 or loss of clinical benefit.	Drug	Toripalimab + Pemetrexed + Anlotinib

Primary outcome

Overall response rate （ORR）
Time frame: two years
Defined as percentage of participants achieving complete response (CR) and partial response (PR) assessed by the Independent Review Committee (IRC) according to the RECIST 1.1

5 secondary outcomes

Progression-free survival (PFS)
Time frame: two years
Overall survival (OS)
Time frame: two years
Disease Control Rate (DCR)
Time frame: two years
Duration of disease response (DOR)
Time frame: two years
overall incidence of adverse events (AE)
Time frame: two years

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2020.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

zhou cheng zhi, Doctor contact

(+86)13560351186

doctorzcz@163.com

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 23 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact zhou cheng zhi, Doctor ((+86)13560351186, doctorzcz@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate （ORR） (time frame: two years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04316351.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2020.