Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Lung Neoplasms

Adenocarcinoma

Mesothelioma

Mesothelioma, Malignant

Adenocarcinoma of Lung

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenoma

Neoplasms, Mesothelial

Pleural Neoplasms

Malignant Mesothelioma

Lung Adenocarcinoma

Nagwa Ahmed, Lecturer

Ahmed Roshdi, Assist. prof

Lung carcinoma is the second most common cancer and a leading cause of cancer-related mortality worldwide. In Egypt, lung carcinoma ranks the 5th among all cancer cases. Malignant mesothelioma is an aggressive neoplasm that arises from mesothelial cells which form the lining of the pleural. There is a strong resemblance between epithelioid mesothelioma and lung adenocarcinoma, some of peripheral lung adenocarcinoma or SCC present with pleurotropic growth like mesothelioma. Glypican-1 (GPC1) is one the six glypican family members. It is one of cell surface heparan sulfate proteoglycans that acts as a growth factor signaling. The aim of this study is to evaluate the immunohistochemical expression of Glypican-1 in pleural epitheloid mesothelioma, lung adenocarcinoma and lung SCC

Lung carcinoma is the second most common cancer and a leading cause of cancer-related mortality worldwide, comprising almost 20% of all cancer deaths. In Egypt, lung carcinoma ranks the 5th among all cancer cases. It is more common in males than females, and most people diagnosed at the age of 65 years or older. The main risk factor of lung malignancy is tobacco smoking.

There are two main histologic variants of lung carcinoma, non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). NSCLC represents more than 80% of all lung carcinomas. Histologically, NSCLC is divided into adenocarcinoma, squamous cell carcinoma (SCC) and large cell carcinoma; of which lung adenocarcinoma is the most common subtype representing about 40%. Specific therapies can be offered to patients based on the histological and molecular status of primary tumors. Therefore, an accurate differentiation between solid predominant lung adenocarcinoma and poorly differentiated lung SCC has become increasingly indispensable; the accurate discrimination of these two main histological types is required for gene-targeted therapy.

Malignant mesothelioma is an aggressive neoplasm that arises from mesothelial cells which form the lining of the pleural, pericardial, and peritoneal cavities. Majority of malignant mesothelioma, approximately 85%, occur in pleural cavity and most of the remainder arising in the peritoneum. In the United States around 3,000 new cases are diagnosed each year. In Egypt, pleural malignant tumors formed 1.3% of total malignant tumors. Pleural mesothelioma is the most frequent primary pleural malignant tumor forming more than half of the cases. The main risk factor for pleural mesothelioma is exposure to asbestos. Other risk factors may include; radiation exposure, old age, male gender and exposure to certain other minerals.

Malignant mesothelioma is divided into three histologic variants that include: epithelioid, sarcomatoid and biphasic variants. Epithelioid variant is the most common subtype representing 70% of malignant mesothelioma. There is a strong resemblance between epithelioid mesothelioma and lung adenocarcinoma, some of peripheral lung adenocarcinoma or SCC present with pleurotropic growth like mesothelioma. The prognosis and management of epithelioid mesothelioma differ from lung carcinoma, so accurate diagnosis of mesothelioma is necessary.

Glypican-1 (GPC1) is one the six glypican family members. It is one of cell surface heparan sulfate proteoglycans that acts as a growth factor signaling. It plays role in the control of cell division and growth regulation. It is encoded by GPC1 gene located at 2q37. It contains 588 amino acids with three predicted heparan sulfate chains. It has been evaluated as a potential target for cancer therapy. Many studies have shown that GPC1 is crucial for efficient cancer cell growth, metastasis and angiogenesis. Glypican-1 overexpression has previously been reported in breast cancer, pancreatic cancer and glioma.

Studies evaluating the expression of Glypican-1 in pleural mesothelioma and lung carcinoma are deficient. Knowledge about its potential value in differentiation between pleural epithelioid mesothelioma, lung adenocarcinoma and SCC needs further elucidation.

Aim of This Work:

The aim of this study is to evaluate the immunohistochemical expression of Glypican-1 in pleural epitheloid mesothelioma, lung adenocarcinoma and lung SCC, and to correlate its expression with some known clinico-pathological parameters, to evaluate its diagnostic and prognostic role.

Glypican-1 Expression in Epithelioid Mesothelioma, Adenocarcinoma and SCC of the Lung

Value of Glypican-1 Expression in Pleural Epithelioid Mesothelioma, Adenocarcinoma and Squamous Cell Carcinoma of the Lung

Sohag University

Lecturer at Pathology Department, Faculty of Medicine, Sohag University

No intervention

Baoxia He, MD

Lung cancer is one of the leading causes of cancer-related deaths in China. Despite advances in systemic therapy and improvement nonsurvival rates for patients with advanced lung cancer, morbidity and mortality remain high.

Recently, many studies reported that patients with positive driving genes such as EGFR(epidermal growth factor receptor,EGFR), ALK(anaplastic lymphoma kinase,ALK), ROS1(c-ros oncogene 1 receptor,ROS1), BRAF (V-raf murine sarcoma viral oncogene homolog B1, BRAF)and so on have clearly targeted drugs, which bring survival benefits to patients. However, about half of patients still lack a clear driving gene target, which may have improved survival due to higher response rates to radiation therapy and other chemotherapy medications.

Development of noninvasive imaging biomarkers such as CT (computed tomography,CT)and MRI (magnetic resonance imaging,MRI)may not only evaluate the response to therapy ,but also could predict the efficacy of drug therapy and whether the driving gene is positive or not, through analysing the relationship between clinical related data and imaging features to find the imaging characteristics for making clinical decisions, and, consequently, contribute to an improved prognosis.

To explore the value of CT and MR using multiple sequences, including T2-TSE-BLADE, T2 maps StarVIBE, and iShim-DWI in evaluating the driving genes and prediction of response to therapy and OS in patients with lung cancer.

Patients with biopsy-proven lung cancer were prospectively enrolled for imaging on CT and a 3T MRI scanner . The MRI protocol included T2-TSE-BLADE, T2 maps,iShim-DWI and StarVIBE sequences, and so on. Patients received treatment according to NCCN( National Comprehensive Cancer Network) guideline. CT and MRI features were analyzed to find the correlation between pretreatment imaging features and driving genes and therapy response. The study will include 400 patients. Inter-reader agreements of TN staging were analyzed excellent for CT and MRI. Diagnostic accuracy of CT and MRI will be calculated separately.

Study of CT and MR in the Lung Cancer

Clinical Study of CT and MR in Prediction of Driving Genes and Response in Patients With Lung Cancer

Retrospectively reviewed data for patients diagnosed with lung cancer . All patients had received a histopathologic diagnosis of lung cancer based on bronchoscopic, percutaneous needle-guided, or surgical biopsies and had undergone gene mutation studies. Analysed the relationship between clinical related data(driving genes and response) and imaging features.

To construct a model,a depth convolution neural network based on MSCT and multi-modal MR quantitative images which can automatically mine key images characterization, combined with imaging features,driving genes and prognosis,could further help to improve the prediction of response and OS of lung cancer treated with systematic therapy .

Henan Cancer Hospital

Patients in the intervention arm will receive up to three rounds of EC treatment (no more than one round annually) to all their HGLs identified at baseline. Follow-up is the same as for Control Arm patients: a bronchoscopy surveillance visit at 6, 12, 24, and at 36 months post-randomisation; with further bronchoscopy surveillance visits at 18 and/or at 30 months post-randomisation (dependent on lesion appearance).

Patients randomised to the surveillance (Control Arm) will have: bronchoscopy surveillance at 6, 12, 24, and at 36 months post-randomisation; with further bronchoscopy surveillance visits at 18 and/or at 30 months post-randomisation (dependent on lesion appearance).

For the purposes of the trial, one round of EC treatment consists of two individual EC treatments with a post-EC bronchoscopy in between to check for a response to the 1st EC treatment. Within each round, the second EC treatment will only be administered if the post-treatment bronchoscopy confirms presence of persistent high grade disease. Patients in the intervention arm will receive up to three rounds of EC treatment (no more than one round annually) to all their HGLs identified at baseline.

Electrocautery Ablation (EC)

EARL Trial Coordinator

This study evaluates whether EC treatment is effective in delaying the progression of high-grade lung lesion(s) to invasive lung cancer. Participants will be randomised to receive either electrocautery (EC) treatment with bronchoscopy surveillance (=intervention), or bronchoscopy surveillance alone (=control) in a 2:1 ratio.

Squamous cell carcinoma of the lung develops through a transition of progressive cytological aberration, from normal to metaplasia, mild, moderate, and severe dysplasia and then carcinoma in situ (CIS) before becoming an invasive cancer. Progression rates to invasive carcinoma can vary depending on the initial grade of the lesion and it is generally accepted that high-grade lesions are more likely to progress to invasive cancer than low-grade lesions. Early detection and treatment of these lesions is critical to improving survival. There is no evidence base examining how, or whether these high-grade lesions (HGLs) should be treated, resulting in diverse treatment practices both nationally and internationally. This is the first randomised clinical trial of a bronchoscopic intervention in treating HGLs using EC.

EARL is a phase II/III multicentre 2:1 randomised controlled trial to evaluate the effectiveness of electrocautery (EC) in the treatment of high-grade lesions of the lung. All patients consented/registered onto the trial will have an bronchoscopy (AFB or NBI) to check for high-grade lesions (HGLs) in the lung, as verified by tissue biopsy. Only patients with ≥1 lung histologically confirmed lung HGL will be randomised to receive either electrocautery ablation (EC) treatment and bronchoscopy surveillance (= intervention), or bronchoscopy surveillance (= control).

The principal objective of the main phase II trial is to demonstrate that airway High-Grade Lesions (HGLs) that are treated with electrocautery are less likely to progress to lung cancer compared to HGLs that are not treated with electrocautery.

Electrocautery Ablation for the Prevention of Lung Cancer

The time to progression of any index HGL in a patient to invasive lung cancer

Cancer Research UK

University College, London

Neoplasms, Squamous Cell

All Drugs and Chemicals

Antibodies

Immunoglobulins

administration of bispecific PSAMxCD3 Ab CC-1.

CC-1 and Toczilizumab

This trial is a phase I study in patients with metastatic non-small-cell lung cancer (NSCLC) after failure of second line therapy aiming to evaluate safety and efficacy of CC-1, a bispecific antibody (bsAb) with PSMAxCD3 specificity developed within DKTK. CC-1 binds to human prostate-specific membrane antigen (PSMA) on tumor cells of squamous cell carcinoma of the lung (SCC) as well as to tumor vessels of SCC, thereby allowing for a dual mode of anti-cancer action. CC-1 was developed in a novel format which not only prolongs serum half-life but most importantly reduces off-target T cell activation with expected fewer side effects. Together with preemptive IL-6 receptor (IL-6R) blockade using tocilizumab, this allows for application of effective bsAb doses with expected high anticancer activity. The study comprises two phases: The first phase is a dose-escalation phase with concomitant prophylactic application of tocilizumab to evaluate the maximally tolerated dose (MTD) of CC-1. This is followed by a dose-expansion phase (also with prophylactic IL-6R blockade using tocilizumab). A translational research program comprising, among others, analysis of CC-1 half-life and the induced immune response as well as molecular profiling in liquid biopsies will serve to better define the mode of action of CC-1 and to identify biomarkers for further clinical development.

SCC of the lung is an aggressive malignant disease with poor prognosis after failure of established therapies. Any drug employed after second-line treatment is associated with only limited clinical benefit. Therefore, there is a high medical need for new therapeutic approaches in this patient population. The clinical effects of immune checkpoint inhibitors in NSCLC have proven the potential of T-cell based immunotherapy in this entity. The rationale for the therapeutic use of CC-1 is based on its proposed mode of action as a bsAb being specifically designed to direct T cells via its CD3 binding part towards tumor target cells via its PSMA binding part. Furthermore, CC-1 also reacts with tumor vessels of NSCLC thereby allowing for a dual mode of anti-cancer action by also attacking tumor blood supply and allowing for improved influx of immune effector cells. Due to its unique ability to redirect T cells via CD3 for PSMA-expressing tumor cell lysis, CC-1 can elicit repeated target cell elimination by cytotoxic T cells and a polyclonal response of previously primed CD4+ and CD8+ T cells. Compared to other immunotherapeutics presently being approved or in development (bsAbs with alternative formats like the authorised bsAb blinatumomab or other antibodies or CAR T cells), CC-1 is expected to offer the following major advantages:

(i) Reduction of off-target T cell activation and thus reduction of side effects due to its optimized format (ii) The possibility to tightly steer anti-target activity via serum level-controlled antibody application which, in contrast to CAR T cells, allows for termination of activity if desired.

On the background of the poor prognosis of patients with SCC of the lung after second-line therapy, the bsAb CC-1 holds promise as a new treatment option of immunotherapy for these patients.

The planned study will include patients with SCC of the lung with detectable PSMA expression on tumor cells after second line treatment. PSMA expression is to be determined by central immunohistochemical assessment of fresh or kryopreserved tumor samples. Only patients with proven PSMA expression on tumor cells as defined by ≥10% positivity of tumor cells can be included. The requirement of ≥10% positivity of tumor cells for PSMA expression cells is in line with definitions of positivity for target antigen expression employed for other antibodies used in cancer treatment, for example the human epidermal receptor protein-2 (HER2)-specific antibodies trastuzumab and pertuzumab. Both antibodies are approved for the treatment of HER2-positive breast cancer, and HER2 positivity is given if ≥10% of tumor cells show staining for HER2 as assessed by immunohistochemistry .

PSMA-positivity is estimated for about 50% of screened patients with SCC of the lung.

Further as a translational research program the investigators implemented PSMA-PET CTs at different time points. PSMA positivity in PSMA-PET CT has been described on several tumor entities including tumors of the lung. In line, PSMA expression has been described on tumor cells and neovasculature of tumor in lung cancer, especially SCC of the lung. However, a correlation of PSMA-PET positive tumors with immunhistochemical PSMA evaluation has so far not been described.

The implementation of PSMA-PET as additional imaging to routine CT, will further improve treatment for patients with SCC of the lung as results of PSMA-PET may replace biopsy in future patients. A maximum of three PSMA-PET CTs may be performed.

Study rationale with regard to objectives and further development of CC-1

In nonclinical studies, in vitro and in vivo, proof of concept, preliminary PK and PK/PD effects as well as toxicology have been evaluated. However, due to differences between animal models and the human situation, some aspects have to be assessed and further characterised in humans. For example, the target mediated drug disposition (TMDD), an effect that largely influences the serum half-life of antibody molecules particularly at low concentrations, cannot be properly addressed in mice. Furthermore, non-human primates (NHP) and rodents have several limitations as predictive models for toxicity and immunogenicity evaluation of CC-1. The CD3 binding part of CC-1 does not cross-react with CD3 of macaques and thus it is not possible to evaluate in these NHPs dose limiting side effects. Likewise, although CC-1 is cross-reactive with macaque-PSMA, PSMA distribution in macaques significantly differs from that in humans. The same holds true for rodents.

Due to the high medical need for patients with SCC of the lung after second-line treatment, the planned phase I trial is designed to confirm and further explore the safety and tolerability of the PSMAxCD3 bsAb CC-1 in adult patients with SCC of the lung. The primary objective is incidence and severity of adverse events (AEs) under therapy with CC-1. Furthermore, the trial aims to expand experience on pharmacokinetics, pharmacodynamics and toxicology of CC-1 from nonclinical studies to the human situation in relation to the PK, expected efficacy and safety. A focus will be on the following specific aspects/parameters:

* Pharmacokinetics and pharmacodynamics of CC-1 in humans
* Immunogenicity of CC-1 in humans based on both absolute (number and percentage of subjects who develop human anti-human antibody (HAHA).
* Absolute changes from baseline in laboratory parameters
* Change in cytokines from baseline
* Assessment of response rate by RECIST on routine imaging
* Evaluation of PSMA PET CT in a translational research program
* Overall and progression free survival

Rationale for preemptive IL-6R blockade by Tocilizumab

As described above, in the planned study the investigators exploit the strategy to use tocilizumab rather to prevent development of CRS in the first place than to treat CRS once it has arisen.

This strategy holds promise to increase the safety of study patients and timely study conduct. By starting the study treatment with CC-1 directly with prophylactic tocilizumab, all study patients will benefit from the expected advantage of this combination with regard to safety and can be treated with sufficiently high doses of CC-1 to achieve dose levels high enough to hopefully result in efficacy effects.

The rationale for preemptive IL-6R blockade by tocilizumab treatment is based on i. The firmly established efficiency and safety of tocilizumab for the treatment of CRS

ii. Lack of clear evidence for increased tumor growth as potential drawback of IL-6R blockage iii. Observations that IL-6 activity, while being responsible for the undesirable sequelae of CRS, appears not to be required for the therapeutic activity of CC-1 CRS that was induced by therapy with the approved bsAb blinatumomab was reported to be successfully treated by tocilizumab. Most importantly, despite rapid disappearance of clinical CRS symptoms, the therapeutic activity of the bsAb blinatumomab was maintained. Furthermore, tocilizumab was also used in the very recent FIH study with the REGN1917 (CD20xCD3) antibody.

Our own nonclinical studies demonstrate that tocilizumab does not impair the therapeutic activity of CC-1, neither in vitro nor in vivo. This is in contrast to steroids which are currently recommended and used as pre- and concomitant treatment to prevent CRS upon blinatumomab therapy.

Due to the mechanism of action of tocilizumab, there is a theoretical risk of tumor development or tumor progression due to immune modulation. On the basis of the current literature derived from large studies conducted in Japan, the USA and Europe, however, there is no evidence for an increased tumor risk upon application of tocilizumab. Only one Japanese study described a minimally increased risk of de novo lymphoma development. However, this could not be confirmed in any other study. Especially for lung cancer, there is no evidence for an increased incidence rate. Interestingly, high systemic IL-6 levels are associated with dismal prognosis in NSCLC. Furthermore, tocilizumab is currently being investigated in several Phase I/II studies for the treatment of solid and hematological neoplasia without evidence for an influence on tumor pathophysiology. Based on these findings, no relevant negative effects of tocilizumab on the efficacy and safety of CC-1 are expected.

Open-label, multicenter dose escalation and dose expansion phase I trial, designed to gain evidence of maximally tolerated and recommended phase-II dose of CC-1 in adult patients with SCC of the lung

Bispecific PSMAxCD3 Antibody CC-1 in Patients With Squamous Cell Carcinoma of the Lung

PPhase-I Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of the Bispecific PSMAxCD3 Antibody CC-1 as Single Agent and Combined With Checkpoint Blockade in Patients With Squamous Cell Carcinoma of the Lung

Correlation with immunhistochemical proven PSMA expression on tumor at baseline

• Value of PSMA-PET-CT in the context of treatment with CC-1 and progressive disease will be performed in terms of a translational research program to correlate PSMA expression as assessed by cryobiopsy with PSMA imaging. PSMA-PET CT will be performed at baseline, EOSf and at any time point during study treatment (cycle 1-6) if progressive disease is assumed in routine imaging, next imaging will be amended by PSMA-PET. Thus, a minimum of 2 and maximum of 3 PSMA-PET-CTs will be performed per patient.

Incidence and severity of adverse events (AEs) (CTCAE V5.0) over 22 days (i.e. until end of first treatment cycle)

Full hematology assessments for safety hemoglobin, red blood cells, platelets, mean cell volume, mean cell hemoglobin concentration, mean cell hemoglobin, white blood cells, absolute differential white cell count and absolute neutrophil count or segmented neutrophil count and Band forms should be performed at each visit and when clinically indicated.

Biochemistry assessments for safety:

sodium, potassium, calcium, magnesium, glucose, creatinine, total bilirubin, gamma glutamyltransferase, alkaline phosphatase,aspartate transaminase, alanine transaminase, urea or blood urea nitrogen, total protein, albumin and lactic dehydrogenase are performed.

To define the recommended phase-II dose of CC-1 under preemptive IL-6R blockade

I

Number and percentage of subjects who develop HAHA at day 15 of every cycle and End Of Safety follw-up (day 43 of last cycle of a given patient) as compared to baseline.

n case of CC-1 in this study, AESIs include cytokine-release syndrome (CRS) as the major "class toxicity" for bsAbs, anaphylactic reactions and immunogenicity of the drug substance

With regard to trial schedule and AESI occurrence, AESIs constitute:

* CRS (i.e. within treatment period)
* Anaphylactic reactions upon study drug administration (i.e., within 24h)
* Development of anti-CC-1 antibodies (HAHA) (day 15, day 43)

AESIs are always be addressed as part of the patient safety report to the DSMB, also non-occurrence will be mentioned . Depending on severity of the AESI, dose reduction or discontinuation of treatment (DLT) may be necessary. Of note, allergic /anaphylactic reactions are not defined as DLT.

Objective tumor response assessed by RECIST on routine imaging at End of safety follow-up and thereafter for 12 months every 3 months.

• For patients receiving more than one cycle objective tumor response will be assessed by RECIST on additional routine imaging every 6 weeks, i.e. prior to the application of cycle 3 (day 22 +/- 5 days of cycle 2) and cycle 5 (day 22 +/-5 days of cycle 4).

Tumor response rate (TRR) The TRR is defined as the percentage of patients with complete remissions (CR) and partial remissions (PR) according to RECIST version 1.1. The TRR will be assessed at 3 and 6 months, as well as every 3 months during the extended treatment period (compare Trial Schedule). For patients receiving additional treatment cycles TRR will be assessed before the application of cycle 3 (day 22 +/- 5 days of cycle 2) and cycle 5 (day 22 +/-5 days of cycle 4).

OS is defined as the time from screening to time of death from any cause. Patients without event are censored at the last date of follow-up.

University Hospital Tuebingen

German Cancer Research Center

Digestive System Diseases

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Head and Neck Neoplasms

Pancreatic Cancer

Anti-Infective Agents

Antineoplastic Agents

Sirolimus

Palbociclib

Gedatolisib

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

* Palbociclib will be administered orally once daily on Days 1-21 for each of the 4-week cycles at a pre-determined dose.
* Gedatolisib will be administered intravenously once weekly on the first day for each of the four weeks during the 4-week cycles at a pre-determined dose.

Palbociclib will be administered orally once daily, 3 weeks out of every 4 in each cycle. The initial dose for part 1 of the study will be 100 mg daily. Dosing will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. No pre-medications for palbociclib are required. It should be administered with food.

Gedatolisib will be administered once weekly on the first day for each of the four weeks during the 4-week cycle. The initial dose for part 1 of the study will be 110 mg. Dosing will be adjusted until Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) are established. No pre-medications for gedatolisib are required.

Geoffrey Shapiro, MD

Rebecca Heist, MD

James Mier, MD

Kailene Sullivan, RN

This research study is studying a combination of drugs as a possible treatment for cancer that might have a specific change in the phosphatidylinositol-3 phosphate (PI3K) pathway.

This research study is an open-label Phase I clinical trial, which tests the safety of an investigational drug or combination of investigational drugs and also tries to define the appropriate dose of the investigational drug(s) to use for further studies. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved Palbociclib for the participant specific disease but it has been approved for other uses. The FDA has not approved Gedatolisib alone or in combination with Palbociclb as a treatment option for the participant's disease.

In this research study the investigators hope to determine if treatment with Palbociclib and Gedatolisib will be tolerated and will help to shrink or stop the growth of the participant's cancer. Palbociclib is an oral drug which has been shown to stop the cell cycle, which is the way a cell initiates growth. Gedatolisib is thought to work by controlling a series of events directing cell growth and survival. Gedatolisib may work to stop or slow activity within tumor cells. By putting these two drugs together the investigators hope that it will have a greater effect on cancer growth than either drug alone.

Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors

Phase I Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors

The dose-escalation schedule will use the mTPI design to discover the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of palbociclib and gedatolisib.

Number of participants with treatment-related adverse events as assessed by version 4.0 of the NCI Common Terminology Criteria for Adverse Events (CTCAE).

Evaluate the preliminary clinical efficacy of palbociclib and gedatolisib in the following expansion cohorts: 1) advanced squamous cell lung cancer, 2) advanced pancreatic cancer, 3) advanced head \& neck cancer, and 4) any tumor with presumed PI3K-pathway dependence using CT and MRI scans per RECIST version 1.

Confirm target engagement of palbociclib and gedatolisib in pre- and on-treatment tumor biopsies from patients enrolled to the MTD expansion cohort through evaluation of changes in immunohistochemical staining for parameters of CDK and PI3K activity.

Evaluate the preliminary clinical efficacy of palbociclib and gedatolisib in advanced solid tumors using CT and MRI scans per RECIST version 1.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Glypican-1 Expression in Epithelioid Mesothelioma, Adenocarcinoma and SCC of the Lung	NCT05228795	Lung Cancer Ade... Lung Cancer Squ... Mesothelioma; L...		-	Sohag University
Study of CT and MR in the Lung Cancer	NCT04034667	Lung Cancer Squ... CT Genes Response MRI	No intervention	18 Years - 80 Years	Henan Cancer Hospital
Electrocautery Ablation for the Prevention of Lung Cancer	NCT03870152	Lung Cancer Squ...	Electrocautery ...	18 Years -	University College, London
Bispecific PSMAxCD3 Antibody CC-1 in Patients With Squamous Cell Carcinoma of the Lung	NCT04496674	Lung Cancer Squ...	CC-1 and Toczil...	18 Years -	German Cancer Research Center
Glypican-1 Expression in Epithelioid Mesothelioma, Adenocarcinoma and SCC of the Lung	NCT05228795	Lung Cancer Ade... Lung Cancer Squ... Mesothelioma; L...		-	Sohag University
Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors	NCT03065062	Lung Cancer Squ... Solid Tumors Head & Neck Can... Pancreatic Canc...	Palbociclib Gedatolisib	18 Years -	Dana-Farber Cancer Institute
Study of the CDK4/6 Inhibitor Palbociclib (PD-0332991) in Combination With the PI3K/mTOR Inhibitor Gedatolisib (PF-05212384) for Patients With Advanced Squamous Cell Lung, Pancreatic, Head & Neck and Other Solid Tumors	NCT03065062	Lung Cancer Squ... Solid Tumors Head & Neck Can... Pancreatic Canc...	Palbociclib Gedatolisib	18 Years -	Dana-Farber Cancer Institute
Study of CT and MR in the Lung Cancer	NCT04034667	Lung Cancer Squ... CT Genes Response MRI	No intervention	18 Years - 80 Years	Henan Cancer Hospital

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