Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lung Neoplasms

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Crizotinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

* The research study procedures include screening for eligibility and study treatment. Study treatment will include evaluations, biopsies, and follow up visits.
* Phase 1 (the dose-finding portion of the study) will follow a standard 3+3 design. Enrollment to the different study arms will occur in parallel.

  * Lorlatinib will be administered orally once daily at a predetermined dose for 28 days
  * Crizotinib will be administered orally twice daily at a predetermined dose for 28 days
* Phase II patients will be treated with Lorlatinib and Crizotinib at a dose recommended based on the phase I study.

* The research study procedures include screening for eligibility and study treatment. Study treatment will include evaluations, biopsies, and follow up visits.
* The phase I part of the study will follow a standard 3+3 design. Enrollment to the different study arms will occur in parallel.

  * Lorlatinib will be administered orally once daily at a predetermined dose for 28 days
  * Binimetinib will be administered orally twice daily at a predetermined dose for 28 days.
* Phase II patients will be treated with Lorlatinib + Binimetinib at a dose recommended based on the phase I study.

* The research study procedures include screening for eligibility and study treatment. Study treatment will include evaluations, biopsies, and follow up visits.
* The phase I part of the study will follow a standard 3+3 design. Enrollment to the different study arms will occur in parallel.

  * Lorlatinib will be administered orally once daily at a predetermined dose for 21 days
  * TNO155 will be administered orally once daily at a predetermined dose for 14 out of 21 days.
* Phase II patients will be treated with Lorlatinib + TNO155 at a dose recommended based on the phase I study.

Lorlatinib will be taken orally once daily for 28 days when combined with crizotinib or binimetinib. Lorlatinib will be taken orally once daily for 21 days when combined with TNO155.

Crizotinib taken orally twice daily for 28 days.

Lorlatinib

Crizotinib will be taken orally twice daily for 28 days.

Binimetnib taken orally twice daily for 28 days.

Binimetinib will be taken orally twice daily for 28 days.

Binimetinib

TNO155 will be taken orally once daily for 14 days.

TNO155

Ibiayi Dagogo-Jack, MD

Elizabeth Kennedy

Ibiayi Dagogo-Jack

Daniel Costa, MD

This research study is evaluating Lorlatinib in combination with Crizotinib, Binimetinib, or TNO155 as a possible treatment for either anaplastic lymphoma kinase (ALK)-positive lung cancer or ROS1-positive lung cancer.

* This research study involves four study drugs.
* Lorlatinib
* Binimetinib
* Crizotinib
* TNO155

This is a Phase I/II clinical trial of three investigational combinations for treatment of either anaplastic lymphoma kinase (ALK)-positive or ROS1-positive lung cancer. The three drug combinations being tested are (1) Lorlatinib combined with Crizotinib and (2) Lorlatinib combined with Binimetinib and (3) Lorlatinib combined with TNO155.

* Lorlatinib is an oral ALK and ROS1 inhibitor. The US Food and Drug Administration (FDA) has approved Lorlatinib for treatment of ALK-positive lung cancer. The FDA has not approved Lorlatinib for treatment of ROS1-positive lung cancer.
* Crizotinib is an oral ALK and MET inhibitor. The FDA has approved Crizotinib for treatment of ALK-positive lung cancer. Crizotinib is not approved by the FDA for the treatment of MET-positive lung cancer. This study will test crizotinib's ability to block MET signaling. Crizotinib is not approved by the FDA for treatment of ROS1-positive lung cancer.
* Binimetinib is an oral MEK inhibitor. The FDA has not approved binimetinib for treatment of ALK-positive or ROS1-positive lung cancer but it has been approved for other uses.
* TNO155 is an oral SHP2 inhibitor. The FDA has not approved TNO155 for the treatment of any disease, including ALK-positive or ROS1-positive lung cancer. It is an investigational drug.
* The FDA has not approved the combination of Lorlatinib with Binimetinib, Crizotinib, or TNO155 as a treatment for any disease.

The research study procedures include screening for eligibility and study treatment which will include evaluations and follow up visits.

* Patients will undergo screening and those who fulfill the eligibility criteria will be assigned to receive either the combination of Lorlatinib and Crizotinib, the combination of Lorlatinib and Binimetinib, or the combination of Lorlatinib and TNO155. Patients with ALK-positive or ROS1-positive lung cancer who have extra copies of the MET growth signal (MET amplification) will be assigned to receive the Lorlatinib and Crizotinib combination. All other patients will be randomly assigned to receive one of the combinations.
* This study consists of 2 parts:

  * Phase I:

    * The investigators are looking to determine whether combining Lorlatinib with either Binimetinib, Crizotinib, or TNO155 is well tolerated and to understand how treatment with the two drugs affects cancer cells and impacts growth signals.
    * Not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well the dose was tolerated.
  * Phase II:

    * The Phase II study will test the safest doses of the combinations (as established in the Phase I study) in a larger group of patients.
    * It is expected that about 96 people will take part in this research study

Lorlatinib Combinations in Lung Cancer

A Phase IB/II Study of Lorlatinib Combinations in Anaplastic Lymphoma Kinase-Rearranged Lung Cancer

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

The highest dose of the combinations that does not cause unacceptable side effects. The maximum tolerated dose is determined in clinical trials by testing increasing doses in different groups of patients until the highest dose with acceptable side effects is found.

Objective response rate (partial and complete responses) will be evaluated according to RECIST v1.1 criteria.

Number of patients with treatment-related side effects, according to CTCAE v5.0

PFS will defined as the time from the start of treatment to the date of the first documented progression or death due to disease. The distribution of PFS will be estimated using the Kaplan-Meier method.

Duration of response to treatment is measured from the time that measurement criteria (RECIST v1.1) are met for complete response or partial response (whichever is recorded first) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started), or death due to any cause.

Array BioPharma

Pfizer

Massachusetts General Hospital

Principal Investigator

Symptoms and General Pathology

Carcinoma, Non-Small-Cell Lung

Recurrence

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antirheumatic Agents

Analgesics

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Nivolumab

Interleukin-2

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Analgesics, Non-Narcotic

Nivolumab infusion every 3 weeks prior to lymphodepletion chemotherapy with cyclophosphamide/fludarabine, TIL infusion and interleukin-2. Then nivolumab infusion every 4 weeks up to 12 months.

Tumor harvest for TIL growth in the lab: A sample of the participant's tumor will be collected and sent to the lab for TIL growth. TIL will be prepared and cryopreserved.

Tumor-infiltrating Lymphocytes (TIL)

Nivolumab (Opdivo®), 360 mg, IV infusion every 3 weeks prior to TIL infusion, and then after TIL infusion 480 mg ever 4 weeks for up to 12 months.

Cyclophosphamide will be administered on days -7 and -6.

Fludarabine will then be infused per institutional standard on Days -7 to -3.

On day 0, all patients will receive a dose infusion TIL cells.

Tumor-infiltrating Lymphocyte Therapy

Participants will receive IL-2 for up to 6 doses, based on participants tolerance and investigator judgement. This will be given after the infusion of the T-cells.

Interleukin-2 (IL2)

Ben Creelan

Tanner Pearson

Ben Creelan, MD, MS

Daniel Abate Daga, PhD

To determine the effect of a special preparation of cells, called tumor-infiltrating lymphocytes (TIL) stimulated with CD40L, when given with the drug nivolumab, for patients with EGFR, ALK, ROS1, or HER2-genomically altered lung cancer.

Clinical Trial of CD40L-Augmented TIL for Patients With EGFR, ALK, ROS1 or HER2-Driven NSCLC

Clinical Trial of CD40L-augmented Tumor Infiltrating Lymphocytes (CD40L TIL) for Patients With Oncogene-Driven Advanced Non-Small Cell Lung Cancer (NSCLC)

To characterize the safety profile of CD40L-augmented TIL administered with nivolumab.

Proportion of patients with complete response + partial response (CR+PR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

The time from the date of the first documentation of initial response (CR or PR) to the date of the first documentation of progressive disease (PD) or death due to any cause.

The time length of patients living from the date of TIL infusion

H. Lee Moffitt Cancer Center and Research Institute

Micronutrients

Hematinics

Vitamins

Carboplatin

Etoposide

Osimertinib

Pemetrexed

Cisplatin

Durvalumab

Etoposide phosphate

Alectinib

Gefitinib

Necitumumab

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

The patients in this group will receive osimertinib taken in combination with savolitinib

The patients in this group will receive osimertinib taken in combination with gefitinib

The patients in this group will receive osimertinib taken in combination with necitumumab

The patients in this group will receive platinum-containing doublet (carboplatin + pemetrexed) taken in combination with durvalumab.

Patients in this group will not receive study treatment but receive further anticancer care (Standard of Care therapy or other experimental therapies) or supportive care, as clinically indicated, in accordance with local practice.

With Group C, the aim is to understand the clinical course and/or outcome for the overall clinical population after progression on first-line monotherapy with osimertinib.

The patients in this group will receive osimertinib taken in combination with alectinib

The patients in this group will receive osimertinib taken in combination with selpercatinib

The patients in this group will receive platinum-containing doublet (etoposide + carboplatin or cisplatin) taken in combination with durvalumab.

The patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin).

The patients in this group will receive osimertinib taken in combination with selumetinib

The patients in this group will receive osimertinib taken in combination with datopotamab deruxtecan.

Osimertinib given orally at 80 mg once daily

Savolitinib will be given orally at 300 mg or 600mg once daily

Savolitinib

Gefitinib given orally at 250 mg once daily

Necitumumab given IV at 800 mg on Day 1 and Day 8 of every 3-week cycle

Durvalumab given IV at 1500 mg on Day 1 of every cycle

Carboplatin given IV on Day 1 of every 21-day cycle for up to 6 cycles

Pemetrexed given IV at 500 mg/m2 body BSA on Day 1 of every cycle

Alectinib given orally at 600mg twice daily and for Japanese patients at 300mg twice daily.

Selpercatinib given orally at 160mg twice daily

Selpercatinib

Selumetinib given orally at 75 mg twice daily for 4 days, followed by 3 days off treatment

Selumetinib

Etoposide 80-100 mg/m2 given IV on day 1, 2 and 3 of every 21-day cycle for up to 4 cycles.

Cisplatin 75-80 mg/m2 given IV on days 1 of each cycle

Datopotamab deruxtecan given IV at 4 or 6 mg/kg on Day 1 of every 3-week cycle.

Datopotamab deruxtecan

Helena A Yu, MD

Phase 2 Platform Study in Patients with Advanced Non-Small Lung Cancer who progressed on First-Line Osimertinib Therapy. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.

This is an open-label, multicentre, multi-drug, biomarker-directed Phase 2 platform study in patients with advanced non-small cell lung cancer (NSCLC) harbouring an epidermal growth factor receptor (EGFR)-sensitizing mutation whose disease has progressed on first-line monotherapy with osimertinib.Treatment options for these patients are limited. Novel treatments for these patients are urgently required.

This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.

Phase 2 platform study in patients with advanced Non-Small Lung Cancer harbouring an epidermal growth factor receptor (EGFR)-sensitizing mutation with evidence of radiological progression following first-Line osimertinib therapy. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments. The study will be conducted in three groups (Groups A, B and C). Patient allocation to a study treatment within each group will be based on tumour molecular profile. Biomarker positive patients or patients with histologically identifiable neuroendocrine transformation to small cell lung cancer (SCLC) or large cell neuroendocrine carcinoma (NEC) will be allocated to a biomarker-matched study treatment in Group A, patients without a biomarker will be allocated to a study treatment in Group B and patients with a biomarker amenable to therapies not currently available in ORCHARD will be allocated to Group C.

Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)

A Biomarker-directed Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Whose Disease Has Progressed on First-Line Osimertinib Therapy.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

The percentage of patients with a confirmed investigator-assessed complete or partial response according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1. Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond progression).

The time from first dose until the date of objective disease progression or death (by any cause in the absence of progression). Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST (Response Evaluation Criteria In Solid Tumours)1.1 defined disease progression or cessation of study treatment (if treating beyond progression).

The time from the date of first response until date of disease progression or death in the absence of disease progression. Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond progression).

The time from the date of the first dose of study treatment until death due to any cause.

Blood samples will be collected at various timepoints to evaluate the sparse pharmacokinetics of study therapeutic agents.

Blood samples will be collected at various timepoints to evaluate the serial pharmacokinetics of study therapeutic agents

To evaluate safety and tolerability of each study treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Lorlatinib Combinations in Lung Cancer	NCT04292119	Lung Cancer Anaplastic Lymp... ROS1 Rearrangem... Relapsed Cancer MET Amplificati... Resistant Cance... NSCLC	Lorlatinib Crizotinib Binimetinib TNO155	18 Years -	Massachusetts General Hospital
Clinical Trial of CD40L-Augmented TIL for Patients With EGFR, ALK, ROS1 or HER2-Driven NSCLC	NCT05681780	Non Small Cell ... Stage IV Non-sm... Recurrent Non S...	Tumor-infiltrat... Nivolumab Cyclophosphamid... Fludarabine Tumor-infiltrat... Interleukin-2 (...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)	NCT03944772	Non-Small Cell ...	Osimertinib Savolitinib Gefitinib Necitumumab Durvalumab Carboplatin Pemetrexed Alectinib Selpercatinib Selumetinib Etoposide Cisplatin Datopotamab der...	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for ros1 rearrangement