Neoplasms

All Conditions

Symptoms and General Pathology

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

INGN 201

Introgen Therapeutics, Inc.

Karen Duvall

James Suen, MD

Brittney Hines

Madeleine Kane, MD

Andrea Gachupin-Garcia

Jarrad Goodwin, MD

Daniela Neamtu

John Hamm, MD

Lauren Titus

Marshall Levine, MD

Justin Reynolds

William Hrushesky, MD

Arlen Waclawczyk

John Nemunaitis, MD

Aida Berryman

Gary Clayman, MD

Kerstin Menander, MD

Julie L Sicam, MT (ASCP) MSHS

There is a need for more treatment options for patients with recurrent squamous cell cancer of the head and neck (SCCHN). These tumors usually have a variety of genetic defects that include disruption of the p53 pathway, a pathway that would ordinarily work to prevent the development of tumors. In this study the transfer of the p53 gene to tumor cells using a modified adenovirus (INGN 201) in combination with chemotherapy (cisplatin and fluorouracil) will be compared to chemotherapy with cisplatin and fluorouracil in patients who have failed surgery and radiotherapy.

Effectiveness and Safety of INGN 201 in Combination With Chemotherapy Versus Chemotherapy Alone

Introgen Therapeutics

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Decitabine

Nivolumab

Decitabine and cedazuridine drug combination

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antimetabolites

Enzyme Inhibitors

Oral decitabine (ASTX727) will be administered during D1-5 (DL1) or D1-4 (DL1-1) followed by Nivolumab on D8 with every 4 week cycle. The expected minimum treatment cycle is 2 and maximum treatment cycle of 6. However, treatment can be continued until disease progression.

Oral decitabine (ASTX727) will be administered during D1-5 (DL1) or D1-4 (DL1-1).

INQOVI (decitabine and cedazuridine)

Nivolumab will be administered on D8 with every 4 week cycle.

Kyunghee Burkitt, DO, PhD

The goal of this clinical trial is to see if the combination of experimental drug ASTX727 and Nivolumab enhances the antitumor immune response in participants will recurrent or metastatic squamous cell carcinoma of the head and neck.

Participants will take a pill called ASTX727 for 4 or 5 days every month followed by an injection of Nivolumab one week after the first dose of study medication.

Anti PD1 inhibitor (Pembrolizumab, Nivolumab) is approved for recurrent/metastatic HNCC. However, response rates to Pembrolizumab or Nivolumab monotherapy are as low as 16-19%, underscoring the presence of immune evasion mechanisms. One of the main immune escape mechanisms described in HNSCC is poor tumor microenvironment characterized by defective HLA class I processing and antigen presentation, which allows tumor cells to evade their detection and destruction by cytotoxic CD8+ T-cells. Mutations or downregulation of the expression of HLA class I component including beta-2- microglobulin (β2M) and antigen processing machinery (APM) genes have been correlated with poor prognosis of HNSCC. Recent studies showed that de novo DNA methylation programs renders terminal T cell exhaustion and subsequent exhausted T cells are refractory to PD-1 blockade mediated rejuvenation. Pretreatment with DNA methyltransferases (DNMT) inhibitor prior to PD-L1 blockade showed enhancement of T cell responses and tumor control during PD-1 inhibitors in mice. A pilot study of novel combination of antiPD-1 and decitabine was conducted in patients with refractory or recurrent AML. The showed a best response of stable disease or better in 6 of 10 patients in patients with R-AML. A phase II clinical trial of anti-PD-1 camrelizumab plus decitabine, in relapsed/refractory Hodgkin lymphoma showed CR rate of 79% with decitabine plus camrelizumab compared to 32% with camrelizumab alone. Based on the promising results of decitabine enhances immune response and antitumor activity shown in both preclinical and preliminary clinical data from the phase II trial of hematological malignancies, I hypothesize that ASTX727 (oral decitabine and cedazuridine) changes DNA methylation status which may enhance the antitumor immune response by modulating tumor immune microenvironment and promoting increased tumor-infiltrating lymphocytes, which may enhance response to anti-PD1 inhibitor in R/M HNSCC patients

ASTX727 and Nivolumab in Squamous Cell Carcinoma of the Head and Neck

Biomarker Driven Phase 1/1b Trial of ASTX727 and Nivolumab in Patients With Recurrent / Metastatic Squamous Cell Carcinoma of the Head and Neck

To find a biologically effective dose of ASTX727 in this clinical trial, levels of global DNA methylation at pre- versus post-ASTX727 will be compared using Wilcoxon signed-rank test.

To investigate the whether DNA methylation status affect immunologic biomarkers, changes in methylation status at pre-, post-ASTX727 and on treatment of ASTX727 plus Nivolumab will be correlated with the changes in immunologic biomarkers.

Establish the maximum tolerated dose (MTD) in Phase I part 1.

Assess safety of ASTX in combination with Nivolumab.

The true objective response rate will be estimated based on the number of responses using a binomial distribution and its confidence interval will be estimated using Wilson's method.

Overall survival will be measured from the date of enrollment to the date of death.

Case Comprehensive Cancer Center

Neoplasm Metastasis

Disease Attributes

Antibodies

Immunoglobulins

Conditionally active biologic anti-ROR2 antibody drug conjugate

Ozuriftamab Vedotin

PD-1 inhibitor

BioAtla Medical Affairs

Azucena Vera

Jacob Thomas, MD

Denise DeMaio

Jamal Misleh, MD

Briana Porwisz

Jochen Lorch, MD

Gracie Smith

Jaspreet Grewal, MD

Justin Alberti

Douglas Adkins, MD

Diana Frias

Winston Wong, MD

OHSU Knight Cancer Institute Clinical Trials

Jeremy Cetnar, MD

Kaitlin Stephens

Jeffrey Russell, MD

This is a multi-center, open-label Phase 2 study designed to evaluate the efficacy and safety of BA3021 in PD-1/L1 failure patients with ROR-2 expression in recurrent or metastatic squamous cell carcinoma of the head and neck.

A Phase 2 Open Label Study of BA3021 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

A Phase 2 Open-Label Study of Ozuriftamab Vedotin (BA3021) in PD-1/L1 Failure Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Proportion of patients who achieve a confirmed CR or PR according to RECIST v1.1

Measured by frequency and severity of adverse events as assessed by CTCAE v5

Time from the first documented OR until the first documented disease progression or death (due to any cause), whichever occurs first

Time from the first dose of IP until the first documentation of disease progression or death due to any cause, whichever occurs first.

All post-baseline disease assessments that occur prior to the initiation of subsequent anticancer therapy

Proportion of patients with a best overall response of confirmed CR, confirmed PR, or stable disease (SD) ≥ 12 weeks.

Time from the first dose of investigational product until the first documentation of OR.

Time from the first dose of BA3021 treatment until death due to any cause.

BioAtla, Inc.

Antibodies, Monoclonal

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Cisplatin

Immunoglobulins, Intravenous

Tubulin Modulators

Antimitotic Agents

TQB2618 injection combined with Penpulimab injection, Paclitaxel, Cisplatin or Carboplatin, 21 days as a treatment cycle. After 4\~6 cycles, TQB2618 injection combined with Penpulimab injection, 21 days as a treatment cycle.

Penpulimab injection combined with Paclitaxel, Cisplatin or Carboplatin, 21 days as a treatment cycle. After 4\~6 cycles, Penpulimab injection, 21 days as a treatment cycle.

TQB2618 injection is an Anti TIM-3 (T-cell immunoglobulin and mucin domain-3) monoclonal antibody.

Penpulimab injection is a humanized Monoclonal Antibody target Programmed Cell Death Protein 1 (PD-1).

Paclitaxel is a anti-microtubule drug, which promotes tubulin polymerization, inhibits depolymerization, maintains tubulin stability and inhibits cell mitosis.

Cisplatin inhibits DNA synthesis by generating in-strand interstrand crosslinking with DNA. Protein and RNA synthesis can also be inhibited.

Carboplatin is a cyclic nonspecific antitumor agents that cause cross-linking between DNA strands and affect their synthesis to inhibit cancer cells.

TQB2618 injection, Penpulimab injection, Paclitaxel, Cisplatin or Carboplatin

Penpulimab injection is a humanized Monoclonal Antibody target Programmed Cell Death Protein 1 (PD-1).

Paclitaxel is a anti-microtubule drug, which promotes tubulin polymerization, inhibits depolymerization, maintains tubulin stability and inhibits cell mitosis.

Cisplatin inhibits DNA synthesis by generating in-strand interstrand crosslinking with DNA. Protein and RNA synthesis can also be inhibited.

Carboplatin is a cyclic nonspecific antitumor agents that cause cross-linking between DNA strands and affect their synthesis to inhibit cancer cells.

Penpulimab injection, Paclitaxel, Cisplatin or Carboplatin

Jun Wang

Fangming Li

Song Qu, Doctor

Jin Wu

YongGui Hong

Zhiye Zhang

Hong Zong, Doctor

Yunfang Chen

Yaqian Han

Jingao Li, Doctor

Zhendong Li, Doctor

XiuHua Sun

To evaluate the efficacy and safety of TQB2618 injection combined with Penpulimab and chemotherapy in the first-line treatment of relapsed/metastatic head and neck squamous cell carcinoma compared to Penpulimab combined chemotherapy.

Progression-free survival (PFS) and objective response rate (ORR) were the primary efficacy endpoints.

A Clinical Trial of TQB2618 Injection Combined With Penpulimab Injection and Chemotherapy Versus Penpulimab Injection Combined With Chemotherapy in First-line Treatment of Relapsed/Metastatic Head and Neck Squamous Cell Carcinoma

A Randomized, Open, Multicenter Phase 1/Phase 2 Clinical Trial of TQB2618 Injection Combined With Penpulimab Injection and Chemotherapy Versus Penpulimab Injection Combined With Chemotherapy in First-line Treatment of Relapsed/Metastatic Head and Neck Squamous Cell Carcinoma

The time period from the first administration of the drug to disease progression or death event (whichever occurs first).

According to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST, the proportion of subjects whose tumors are evaluated as complete response(CR) and partial response(PR) by subcenter imaging evaluation. It is recorded from the first administration of the drug to disease progression or initiation of a new anticancer treatment.

Proportion of survived participants without progression at 9th months.

Time from the randomization to death from all causes.

The percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) for 6 weeks or more as determined by investigators according to RECIST 1.1.

The percentage of participants with complete response (CR), partial response (PR), or stable disease (SD) for 6 months or more as determined by investigators according to RECIST 1.1.

The period from firstly-recorded objective tumor response (CR or PR) to firstly-recorded objective tumor progression or death due to any cause (whichever occurs first).

All adverse medical events that occur after the subject receives the investigational drug may be manifested as symptoms, signs, disease, or laboratory abnormalities, but are not necessarily causally related to the investigational drug, evaluated according to the National Cancer Institute standard for common toxic criteria \[NCI-CTC v5.0\].

All adverse medical events that occur after the subject receives the investigational drug may be manifested as symptoms, signs, disease, or laboratory abnormalities, but are not necessarily causally related to the investigational drug, evaluated according to the National Cancer Institute standard for common toxic reactions \[NCI-CTC v5.0\].

It refers to adverse medical events such as death, life-threatening, permanent or serious disability or loss of function, hospitalization or prolonged hospitalization, and congenital abnormalities or birth defects after the subject receives the experimental drug.

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Herbal and Botanical

Docetaxel

Taxane

Grapefruit Seed Extract

Participants will receive duvelisib by mouth twice daily,dosage per protocol continuously (days 1-21 of a 21-day cycle) with a 7-day lead-in planned prior to the start of taxane therapy.

Docetaxel at via IV will be delivered on day 1 of each 21-day cycle.

Treatment will continue for 24-months or until unacceptable toxicity, progression, or death.

Duvelisib capsules should be swallowed whole with a glass of water (approximately 8 ounces).

Advise patients not to open, break, or chew the capsules. Duvelisib may be administered without regard to meals; however, subjects should avoid grapefruit and grapefruit juice while on duvelisib.

continue for up to 24 months.

Duvelisib

Docetaxel chemotherapy once every 21 days (by intravenous infusion) over about 30- 60 minutes at each visit. This will continue for up to 24 months

Glenn J. Hanna, MD

This trial that is investigating a medication called duvelisib in combination with docetaxel for the treatment of squamous cell carcinoma of the head and neck (SCCHN) that has returned or spread outside the head and neck area.

The names of the study drugs involved in this study are:

* Duvelisib (PI3K inhibitor)
* Docetaxel chemotherapy

This multicenter, phase II open-label, single-arm trial will enroll participants with recurrent or metastatic (R/M), incurable squamous cell carcinoma of the head and neck (SCCHN) who have failed or discontinued PD-1 blockade in the first-line (1L) advanced disease setting, regardless of human papillomavirus (HPV) and smoking status, or PI3K pathway alteration status.

This research study involves the oral (taken by mouth) agent duvelisib with the intravenous (IV) chemotherapy agent docetaxel.

The names of the study drugs involved in this study are:

* Duvelisib (PI3K inhibitor)
* Docetaxel chemotherapy

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

Participants will receive study treatment for up to 2 years and will be followed for 3 years.

It is expected that about 30 people will take part in this research.

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug (duvelisib) to learn whether it works in treating a specific disease. "Investigational" means that the drug is being studied.

The U.S. Food and Drug Administration (FDA) has not approved duvelisib for this specific disease but has approved it for other uses (such as certain types of blood cancers). The FDA has approved docetaxel as a treatment option for head and neck cancer, as well as other cancer types.

Duvelisib Plus Docetaxel In Recurrent/Metastatic HNSCC

A Phase II Study of Duvelisib Plus Docetaxel in PD-1 Inhibitor Experienced Patients With Incurable Head and Neck Squamous Cell Carcinoma

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 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 best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Measured with RECIST v 1.1

Overall Survival (OS) is defined as the time from registration to death due to any cause, or censored at date last known alive

Progression-Free Survival (PFS) is defined as the time from registration to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation.

The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) 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. Participants without events reported are censored at the last disease evaluation).

NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Effectiveness and Safety of INGN 201 in Combination With Chemotherapy Versus Chemotherapy Alone	NCT00041626	Carcinoma, Squa...	INGN 201	18 Years -	Introgen Therapeutics
ASTX727 and Nivolumab in Squamous Cell Carcinoma of the Head and Neck	NCT06357858	Recurrent Squam... Metastatic Squa... Head and Neck S...	INQOVI (decitab... Nivolumab	19 Years -	Case Comprehensive Cancer Center
A Phase 2 Open Label Study of BA3021 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck	NCT05271604	Head and Neck C... Squamous Cell C... Recurrent Squam... Metastatic Canc... Metastatic Squa...	Ozuriftamab Ved... PD-1 inhibitor	18 Years -	BioAtla, Inc.
A Clinical Trial of TQB2618 Injection Combined With Penpulimab Injection and Chemotherapy Versus Penpulimab Injection Combined With Chemotherapy in First-line Treatment of Relapsed/Metastatic Head and Neck Squamous Cell Carcinoma	NCT05783921	Recurrent Squam... Metastatic Squa...	TQB2618 injecti... Penpulimab inje...	18 Years - 75 Years	Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Duvelisib Plus Docetaxel In Recurrent/Metastatic HNSCC	NCT05057247	Squamous Cell C... Recurrent Squam... Metastatic Head... Advanced Head a... Advanced Head a...	Duvelisib Docetaxel	18 Years -	Dana-Farber Cancer Institute
ASTX727 and Nivolumab in Squamous Cell Carcinoma of the Head and Neck	NCT06357858	Recurrent Squam... Metastatic Squa... Head and Neck S...	INQOVI (decitab... Nivolumab	19 Years -	Case Comprehensive Cancer Center
A Phase 2 Open Label Study of BA3021 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck	NCT05271604	Head and Neck C... Squamous Cell C... Recurrent Squam... Metastatic Canc... Metastatic Squa...	Ozuriftamab Ved... PD-1 inhibitor	18 Years -	BioAtla, Inc.
A Phase 2 Open Label Study of BA3021 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck	NCT05271604	Head and Neck C... Squamous Cell C... Recurrent Squam... Metastatic Canc... Metastatic Squa...	Ozuriftamab Ved... PD-1 inhibitor	18 Years -	BioAtla, Inc.

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