Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Head and Neck Neoplasms

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Tubulin Modulators

Antimitotic Agents

IV docetaxel administered once every three weeks as per standard of care. Treatment continues until disease progression, unacceptable toxicity or withdrawal of consent.

Oral PX-866 administered daily at the RD in combination with IV docetaxel administered once every three weeks on a 21 day cycle. Treatment continues until disease progression, unacceptable toxicity or withdrawal of consent.

Oral PX-866, administered daily at the RD in combination with IV docetaxel administered once every three weeks on a 21 day cycle. Treatment continues until disease progression, unacceptable toxicity or withdrawal of consent.

PX-866

Phase 1: To determine the maximally tolerated dose (MTD) or recommended dose (RD) and any potential efficacy of PX-866 in combination with docetaxel in patients with solid tumors.

Phase 2: To determine the antitumor activity and safety of PX-866 in combination with docetaxel versus docetaxel alone in patients with NSCLC or SCCHN.

This is a Phase 1/2 open-label study. In the Phase 1 part of the study, PX-866 was given in combination with docetaxel to patients with incurable locally advanced, recurrent or metastatic cancer.

Phase 2 of the study is an open-label, randomized evaluation of the antitumor activity and safety of PX-866, administered at the MTD/RD identified in Phase 1 (8mg daily), in combination with docetaxel versus docetaxel alone in patients with locally advanced, recurrent, or metastatic NSCLC (Group 1) or patients with locally advanced, recurrent, or metastatic SCCHN (Group 2).

Group 1 (patients with locally advanced, recurrent, or metastatic NSCLC) is now closed to enrollment.

All treatments will be administered on a 21-day cycle. Docetaxel 75 mg/m2 will be administered IV on Day 1 of each 21-day cycle. PX-866 will be administered orally or via PEG tube (if applicable) once per day on Days 1 to 21 of all treatment cycles in patients randomized to the treatment arm containing PX-866.

Patients will be evaluated for progression approximately every 6 weeks. Patients with stable disease (SD) or better, per investigator assessment, will receive repeat cycles of treatment on a 21-day schedule until disease progression, unacceptable toxicity or withdrawal of consent.

Study of PX-866 and Docetaxel in Solid Tumors

Phase 1/2 Study of PX-866 and Docetaxel in Patients With Solid Tumors

Cascadian Therapeutics Inc.

Symptoms and General Pathology

Recurrence

Neoplasms, Squamous Cell

Carboplatin

Cetuximab

Cisplatin

Antineoplastic Agents, Immunological

All participants receive patritumab with cetuximab plus platinum-based therapy (cisplatin or carboplatin)

All participants receive placebo with cetuximab plus platinum-based therapy (cisplatin or carboplatin)

Patritumab initial loading dose is 18 mg/kg IV over 60 minutes followed by a maintenance dose of 9 mg/kg IV over 60 minutes (± 10 minutes) every three weeks

Patritumab

Cetuximab 400 mg/mg/m\^2 IV loading dose, followed by 250 mg/m\^2 weekly

Cisplatin at 100 mg/m\^2 IV infused over 1 hour, every three weeks up to a maximum of 6 cycles

Carboplatin IV over 30 to 60 minutes, every 3 weeks for a maximum of 6 cycles

Placebo

Kevin Harrington, Prof, MD

This study will test an investigational study drug called patritumab. It is a 'randomized study' which means participants have an equal chance of being assigned to receive the experimental medication (patritumab) or a substance that looks like the experimental product, but is not (placebo). Patritumab may work when combined with other medications that are approved for the treatment of head and neck cancer. They are called cetuximab, cisplatin or carboplatin. All participants will receive the other medications approved for treatment of head and neck cancer, even if they do not receive the experimental product.

Main objective of the trial:

The main objective of the trial is to evaluate progression-free survival (PFS) in the heregulin (HRG) high expression population from subjects treated with patritumab + cetuximab + platinum-based therapy compared to placebo + cetuximab + platinum-based therapy.

Patritumab With Cetuximab and a Platinum Agent for Squamous Cell Carcinoma (Cancer) of the Head and Neck (SCCHN )

Randomized, Placebo-controlled, Double-blind Phase 2 Study of Patritumab (U3-1287) in Combination With Cetuximab Plus Platinum-based Therapy in First Line Setting in Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at http://www.clinicalstudydatarequest.com. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://www.clinicalstudydatarequest.com/Study-Sponsors-DS-Details.aspx

PFS is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever comes first.

Median PFS is from Kaplan-Meier analysis. Confidence interval (CI) for median was computed using Brookmeyer-Crowley method.

Overall survival (OS) is defined as the time from the date of randomization to death due to any cause

Best overall response rate (ORR) is defined as the percentage of participants with Complete Response (CR) or Partial Response (PR)

Daiichi Sankyo

Total

Age, Continuous

18-64 Years

65-84 Years

Age, Customized

Sex: Female, Male

White

Asian

Other, Not Specified

Race/Ethnicity, Customized

Romania

Belgium

Hungary

Poland

United Kingdom

France

Germany

Region of Enrollment

0=Fully active

1=Restricted in Physically Strenuous Activity

2=Ambulatory and Capable of All Self-Care

Eastern Cooperative Oncology Group (ECOG) Performance Status

Global Clinical Leader

Heregulin-high population - Patritumab vs Placebo

Participants in the heregulin-high expression population

Progression Free Survival (PFS) in the Heregulin (HRG)-High Expression Population

The trial terminated before sufficient data were collected for this analysis (at approximately 12 months which is prior to the time point for this analysis).

Median Overall Survival

Percentage of Participants With Best Overall Response

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Uterine Cervical Neoplasms

Breast Neoplasms

Triple Negative Breast Neoplasms

Pancreatic Neoplasms

Melanoma

Prostatic Neoplasms

Stomach Neoplasms

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Urinary Bladder Neoplasms

Endometrial Neoplasms

Urogenital Neoplasms

Genital Diseases

Urogenital Diseases

Skin Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Uterine Neoplasms

Uterine Diseases

Breast Diseases

Esophageal Cancer

Pancreatic Cancer

Ovarian Cancer

Stomach Cancer

Ovarian Epithelial Cancer

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Groups of patients will receive increasing doses of HMBD-001 as a single agent to find a safe dose that best targets cancer cells. Approximately 26 patients with tumours known to express HER3 will be entered into this arm.

An expansion cohort of up to 25 patients with a confirmed HER3 positive or confirmed NRG1 fusion rearrangement RAS wild type colorectal cancer, castration resistant prostate cancer, triple negative breast cancer or squamous cell head and neck cancer will receive the HMBD-001 single agent RP2D as determined in Part A Arm 1.

Intravenous infusion given over a 21 or 28 day cycle dependent on dosing frequency. Number of cycles: 6 or until disease progression or unacceptable toxicity develops.

HMBD-001

Johann de Bono, Prof

Simon Lord, Dr

Derek Paisley

Johaan de Bono, Prof

This clinical trial is evaluating a drug called HMBD-001 (an anti-HER3 monoclonal antibody) in patients with advanced HER3 positive solid tumours. The main aims are to find out the maximum dose of HMBD-001 that can be given safely to patients alone and in combination with other anti-cancer agents, more about the potential side effects of HMBD-001 and how these can be treated and what happens to HMBD-001 inside the body and how it affects cancer cells.

HMBD-001 is a type of drug called a monoclonal antibody, which works by targeting a protein called HER3, that is found in high numbers in some types of cancers including those which contain NRG1 gene fusions. By attaching itself to this protein it may then work to kill the cancer cells or to stop them growing.

This is a first-in-human clinical trial which has two parts:

Part A is a 'dose escalation' phase where small groups of patients will receive increasing doses of HMBD-001 to find the safest dose which best targets cancer cells.

* In Arm 1, patients will receive HMBD-001 on its own (as a single agent).
* In Arm 2, patients will receive HMBD-001 given with other anti-cancer drugs (in combination).

Part B is a 'dose expansion' phase where larger groups of patients with specific cancer types, known to have high levels of the protein HER3 or a confirmed NRG1 gene fusion will receive the highest doses of HMBD-001 considered to be safe in Part A either alone as single agent or in combination with other anti-cancer drugs.

The main aims of the clinical trial are to find out:

* The highest dose of HMBD-001 alone and in combination with other anti-cancer drugs that can be given safely to patients.
* More about the potential side effects of HMBD-001 when given alone and in combination with other anti-cancer agents and how they can be managed.
* What happens to HMBD-001 inside the body and how it affects cancer cells.
* The potential anti-tumour activity of HMBD-001 as a single agent and in various combination regimens in specific tumour types of HER3 expressing tumours or tumours with NRG1 gene fusions.

HMBD-001 in Advanced HER3 Positive Solid Tumours

HMBD-001 (an Anti-HER3 Monoclonal Antibody) Given Intravenously as a Single Agent and in Combination in Patients With Advanced HER3 Positive Solid Tumours

Recommended dose of HMBD-001 given a) as a single agent and b) in combination with selected anticancer agent(s) with an estimated Dose Limiting Toxicity (DLT) rate that is closest to 25% using a one-stage Bayesian Continual Reassessment Method (CRM)

Number of grade 3, 4 and adverse events related to HMBD-001 given a) as a single agent and b) in combination with selected anti-cancer agent(s) graded according to National Cancer Institute Common Criteria for Adverse Events (NCI CTCAE) Version 5.0

Number of patients achieving a complete response (CR) or partial response (PR) to HMBD-001 based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 in the chosen tumour types

Maximum observed plasma concentration (Cmax) of HMBD-001

Terminal elimination half-life (t½) of HMBD-001

Time taken to reach maximum observed concentration (Tmax) of HMBD-001

Volume of distribution of HMBD-001 in plasma

Number of patients achieving a complete response (CR), partial response (PR) or stable disease (SD) based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1

Number of Patients whose cancer has not progressed at 12 and 24 months

Number of patients who are still alive at 12 and 24 months

Hummingbird Bioscience

Cancer Research UK

Radiation Therapy 60 Gy total dose in 30 fractions: 2.0 Gy/fraction once daily five fractions per week

Cetuximab 400 mg/m2 of body surface area over a period of 120 minutes day 1 250 mg/m2 of body surface area over a period of 60 minutes weekly during radiation

Radiation Therapy 60 Gy total dose in 30 fractions: 2.0 Gy/fraction once daily five fractions per week

Radiation

Heath B Mackley, MD

The standard treatment for head and neck cancer relapses in previously irradiated patients is controversial. Reirradiation has had some success, but many patients still die from their disease. Cetuximab is helpful in relapsed head and neck cancer, and it improves the effectiveness of radiation in some head and neck cancer patients. But, it has not been studied with reirradiation. The purpose of this study is to see the effects, both good and bad, of reirradiation with cetuximab.

Image Guided Intensity Modulated Reirradiation (IG-IMRT) With Cetuximab for Locoregionally Confined Recurrent Head and Neck Squamous Cell Carcinoma

Image Guided Intensity Modulated Reirradiation With Concurrent Cetuximab in the Treatment of Locoregionally Confined Relapsed Squamous Cell Carcinoma of the Head and Neck

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of PX-866 and Docetaxel in Solid Tumors	NCT01204099	Non Small Cell ... Squamous Cell C...	Docetaxel PX-866	18 Years -	Seagen Inc.
Patritumab With Cetuximab and a Platinum Agent for Squamous Cell Carcinoma (Cancer) of the Head and Neck (SCCHN )	NCT02633800	Head and Neck N...	Patritumab Cetuximab Cisplatin Carboplatin Placebo	18 Years -	Daiichi Sankyo
HMBD-001 in Advanced HER3 Positive Solid Tumours	NCT05057013	Bladder Cancer Triple Negative... Castration-resi... Cervical Cancer RAS Wild Type C... Endometrial Can... Gastric Cancer Hepatocellular ... Melanoma Non-small Cell ... Oesophageal Can... Ovarian Cancer Pancreatic Canc... Squamous Cell C...	HMBD-001	16 Years -	Cancer Research UK
Image Guided Intensity Modulated Reirradiation (IG-IMRT) With Cetuximab for Locoregionally Confined Recurrent Head and Neck Squamous Cell Carcinoma	NCT00934518	Squamous Cell C...	Radiation Cetuximab	18 Years -	Milton S. Hershey Medical Center
Study of PX-866 and Docetaxel in Solid Tumors	NCT01204099	Non Small Cell ... Squamous Cell C...	Docetaxel PX-866	18 Years -	Seagen Inc.

Spots Global Cancer Trial Database for squamous cell cancer of the head and neck