Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Skin and Connective Tissue Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Breast Neoplasms

Triple Negative Breast Neoplasms

Head and Neck Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Topoisomerase I Inhibitors

Enzyme Inhibitors

Immunologic Factors

MM-151 Dose escalation frequency - once weekly, once every two weeks, once every three weeks

MM-151 given weekly, irinotecan 180 mg/m2 given once every two weeks

MM-151

MM-151 + irinotecan

This study is a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design, evaluating MM-151 at varying dose levels and frequencies, and subsequently in combination with irinotecan.

This study is a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design exploring weekly, bi-weekly, and tri-weekly dosing schedules. Successive MM-151 monotherapy cohorts of three or more patients will be treated at escalating doses until a maximum tolerated dose is identified, and subsequently in combination with irinotecan. The study consists of three parts as follows: MM-151 monotherapy dose escalation (Part 1); MM-151 monotherapy expansion cohort in cetuximab-refractory colorectal cancer (Part 2); MM-151 + irinotecan dose escalation (Part 3). It is expected that approximately 4 study sites will participate.

Safety Study of the Drug MM-151 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment

A Phase 1 and Pharmacologic Study of MM-151 in Patients With Refractory Advanced Solid Tumors

Merrimack Pharmaceuticals

Digestive System Diseases

Carcinoma

Colorectal Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Cetuximab

Antineoplastic Agents, Immunological

increasing doses of weekly MM-121 + weekly cetuximab

increasing doses of irinotecan + the Recommended Phase 2 Dose/Maximum Tolerated Dose (RP2D/MTD) of MM121 + cetuximab as determined in Part 1

MM-121

Victor Moyo, MD

The purpose of this study was to evaluate the safety and tolerability of escalating doses of the MM-121 plus cetuximab and the MM-121 plus cetuximab plus irinotecan combination.

This study was a Phase 1 and pharmacologic dose-escalation trial of MM-121 plus cetuximab plus irinotecan. The study assessed the safety, tolerability, and pharmacokinetics of MM-121, cetuximab and irinotecan.

A Safety Study of MM-121 With Cetuximab and Irinotecan in Patients With Advanced Cancers

A Phase 1 Study of MM-121 in Combination With Cetuximab and Irinotecan in Patients With Advanced Cancers

To establish the safety of escalating doses of MM-121 in combination with cetuximab or in combination with cetuximab and irinotecan in order to determine the recommended phase 2 dose.. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD.

Using a 3+3 dose escalation model, the maximum tolerated dose of each combination was determined by assessing dose-limiting toxicities in each cohort. RP2D = one dose lever lower than the MTD

Part 1:

Cohort 1: MM-121: 12 mg/kg MM-121 QW + Cetuximab: 400 mg/m2 loading dose/200 mg/m2 (400/200) QW maintenance Cohort 2a: MM-121: 20 mg/kg IV QW + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 2b: MM-121: 12 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 3a: MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW (40/20) + Cetuximab: 400 / 200 mg/m2 maintenance IV QW Cohort 3b: MM-121 20 mg/kg IV QW + Cetuximab: 400 /250 mg/m2 maintenance IV QW Cohort 4: MM-121: 40/20 mg/kg IV QW + Cetuximab: 400 / 250 mg/m2 maintenance IV QW

Part 2:

Cohort 1: MM-121: 20 mg/kg IV QW + Cetuximab: 400/200 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2 IV Q2W Cohort 2: MM-121: 40 / 20 mg/kg IV QW + Cetuximab: 400/250 mg/m2 maintenance IV QW + Irinotecan: 180 mg/m2

To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response (PR) is defined as \>20% decrease in tumor burden from baseline and a Complete Response (CR) is defined as complete disappearance from tumor burden from baseline. Objective Response is presented as the total # patients with PR or CR.

Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first six weeks of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the maximum observed concentration (Cmax). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (12 mg/kg, 20 mg/kg, or 40/20 mg/kg) and per study part (Part 1 or Part 2)

Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first six weeks of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the AUClast. Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (12 mg/kg, 20 mg/kg, or 40/20 mg/kg) and per study part (Part 1 or Part 2)

Samples were collected to determine the presence of an immunologic reaction to MM-121 (i.e. human anti-human antibodies).

Sanofi

All related AEs ongoing at the time of treatment discontinuation were followed until resolution. Investigators were to report any AEs/SAEs assumed to be related any time, even if occurring more than 30 days after last dose. Though different for each patient, on average, patients could be followed for related AEs/SAEs for \~1 year after termination

increasing doses of weekly MM-121 + weekly cetuximab

MM-121 (SAR256212): MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Cetuximab: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Part 1: MM-121 + Cetuximab

increasing doses of irinotecan + the RP2D of MM121 + cetuximab as determined in Part 1

MM-121 (SAR256212): MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Irinotecan: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Cetuximab: MM-121 (SAR256212) (IV) plus Cetuximab (IV) and Irinotecan (IV)

Part 2: MM-121 + Cetuximab + Irinotecan

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Clinical Trial Manager

MM-121: 12 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW

Part 1: Cohort 1

MM-121: 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW

Part 1: Cohort 2a

MM-121: 12 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

Part 1: Cohort 2b

MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW

Part 1: Cohort 3a

MM-121: 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

Part 1: Cohort 3b

MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

Part 1: Cohort 4

MM-121: 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW Irinotecan: 180 mg/m2 IV Q2W

Part 2: Cohort 1

MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW Irinotecan: 180 mg/m2 IV Q2W

Part 2: Cohort 2

Patients participating in dose escalation

Dose Escalation: To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Plus Cetuximab and the MM-121 Plus Cetuximab Plus Irinotecan Combination

MM-121 loading dose

MM-121 maintenance dose

Number of patients participating in dose-escalation portion (excluding expansion cohort patients who were not evaluated for DLTs) MTD of cetuximab and irinotecan for the combination(s) are presented in a separate endpoint entry

To Further Determine the Safety Parameters of the MM-121 + Cetuximab and MM-121 + Cetuximab + Irinotecan Combination by Determining the Recommended Phase 2 Dose (RP2D) of the Combination(s) (Via Recording of Maximum Tolerated Dose (MTD)): MM-121 Doses

Cetuximab loading dose

Cetuximab maintenance dose

Number of patients participating in dose-escalation portion (excluding expansion cohort patients who were not evaluated for DLTs and thus not included in determining MTD/RP2D) NOTE: MTD of MM-121 provided in separate endpoint entry

To Further Determine the Safety Parameters of the MM-121 + Cetuximab and MM-121 + Cetuximab + Irinotecan Combination by Determining the Recommended Phase 2 Dose (RP2D) of the Combination(s): Cetuximab and Irinotecan

MM-121: 12 mg/kg IV weekly in 4-week cycles Cetuximab: 400 mg/m2 IV one-time loading dose followed by 200 mg/m2 IV weekly maintenance doses

MM-121: 40 mg/kg one time loading dose followed by 20 mg/kg IV QW Cetuximab: 400 mg/m2 one-time loading dose followed by 250 mg/m2 maintenance IV QW

Part 1: Expansion Cohort

MM-121: 20 mg/kg IV QW

Cetuximab: 400 mg/m2 loading dose followed by 200 mg/m2 maintenance IV QW

Irinotecan: 180 mg/m2 IV Q2W

MM-121: 40 mg/kg loading dose followed by 20 mg/kg IV QW

Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

Irinotecan: 180 mg/m2 IV Q2W

MM-121: 20 mg/kg IV QW

Cetuximab: 400 mg/m2 loading dose followed by 250 mg/m2 maintenance IV QW

Irinotecan: 180 mg/m2 IV Q2W

Part 2: Expansion Cohort

Objective Response Rate

MM-121 mg/kg plus cetuximab at either 400/200 mg/m2 or 400/250 mg/m2

Part 1: 12 mg/kg

MM-121: 20 mg/kg Plus cetuximab at either 400/200 mg/m2 or 400/250 mg/m2

Part 1: 20 mg/kg

MM-121: 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance doses Plus cetuximab at either 400/200 mg/m2 or 400/250 mg/m2

Part 1: 40/20 mg/kg

MM-121: 20 mg/kg plus cetuximab at 400/250 mg/m2 plus irinotecan at 180 mg/m2

Part 2: 20 mg/kg

MM-121: 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance doses plus cetuximab 400/250 mg/m2 plus irinotecan 180 mg/m2

Part 2: 40/20 mg/kg

Pharmacokinetics

Data presented by dose level of MM-121, regardless of the cohort (i.e. 15 patients in Part 1 were administered the 40/20 dose level of MM-121: 3 in cohort 3b, 4 in cohort 4, and 8 in the Part 1 expansion)

Pharmacokinetic Parameters of MM-121

Immunogenicity

Overall Study

Infections

Mouth and Tooth Diseases

Virus Diseases

Xerostomia

Salivary Gland Diseases

Mouth Diseases

Stomatognathic Diseases

AAV2hAQP1

John A Chiorini, Ph.D.

Background:

- Radiation can cause the parotid salivary glands to make less saliva (dry mouth). This can cause problems like infections and tooth decay. Researchers hope a new drug can help people with dry mouth caused by radiation.

Objectives:

- To examine the safety of AAV2hAQP1 gene therapy. To see if the drug increases saliva in people whose parotid glands have had radiation.

Eligibility:

- People at least 18 years of age with a history of radiation therapy for head and neck cancer.

Design:

Participants will be screened in 2 visits with:

* medical history
* physical exam
* scans of the head, neck, and chest
* intravenous administration of glycopyrrolate to stop saliva
* saliva collections
* sialogram which is a procedure in which a substance is injected in the parotid gland and X-rays are taken.
* non-drug infusion
* a small piece of skin being taken

3-5-day hospital stay: Participants will receive the gene infusion. The AAV2hAQP1 will be in a solution in a syringe. It will be slowly pushed into the parotid gland through the parotid duct, an opening in the mouth near the second upper molar tooth.

10 outpatient visits over 3 years. These may include:

* repeats of selected screening tests, including saliva collection
* blood and urine tests
* oral and dental examinations
* head and neck exams, including the use of a thin scope to see the back of the throat
* questionnaires
* a small piece of parotid tissue being taken by either a small scope through the parotid duct or by a small needle guided by ultrasound
* scans of the head and neck. For some, contrast will be injected in a vein
* completion of a diary about how the participant feels between visits
* swabs of teeth and gums to assess the microbiome of the mouth

The treatment of most head and neck cancer patients includes ionizing radiation (IR). Salivary glands in the IR field suffer irreversible damage. There is no conventional treatment available to correct this condition. Our research group has been developing an adeno-associated virus vector based on the hypothesis that this vector is capable of safely transferring the human aquaporin-1 (hAQP1) cDNA gene to parotid glands of adult patients with IR-induced salivary hypofunction, resulting in an elevated salivary output. Human AQP1 is a plasma membrane protein that facilitates water movement across lipid bilayers. Minipig studies have shown that the AAV2hAQP1 strategy for restoring salivary flow to IR-damaged salivary glands is effective without untoward effects after salivary gland delivery. As a proof of concept that AQP1 would restore saliva flow in a human population, we recently completed a phase 1 clinical trial (06-D-0206) using an Adenovirus-based vector encoding AQP1 to a single previously irradiated parotid gland in eleven patients using an open label, single dose, dose-escalation design. All patients tolerated vector delivery and study procedures well and positive objective and subjective responses were seen in five patients, all at doses \<5.8 times10(9) vp/gland. At higher doses the patients possibly initiated an immune response to the vector and no improvement in gland function was observed. These findings have encouraged us to pursue studies with AAV2 based vectors, which have demonstrated lower immunogenicity and more stable expression compared with adenoviral vectors. The purpose of this clinical protocol is to test the safety of AAV2hAQP1, with some measures of efficacy, in adult patients with established IR-induced parotid gland hypofunction. The targeted tissue site for the AAV2hAQP1 vector in the proposed study is a single parotid gland. In this Phase 1 dose-escalation study, safety will be evaluated using conventional clinical and immunological parameters. The primary outcome measure for biological efficacy will be parotid gland salivary output.

Safety of a Single Administration of AAV2hAQP1, an Adeno-Associated Viral Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in People With Irradiation-Induced Parotid Salivary Hypofunction

Open-Label, Dose-Escalation Study Evaluating the Safety of a Single Administration of an Adeno-Associated Virus Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in Individuals With Irradiation-Induced Parotid Salivary Hypofunction

National Institute of Dental and Craniofacial Research (NIDCR)

MeiraGTx, LLC

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Death

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasm Metastasis

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Immunomodulating Agents

Antibodies, Bispecific

Participants will receive PF-07257876 at escalating dose levels.

Participants with non-small cell lung cancer (NSCLC) will receive PF-07257876 at the recommended dose from Part 1.

Participants with squamous cell carcinoma of the head and neck (SCCHN) will receive PF-07257876 at the recommended dose from Part 1.

PF-07257876

Pfizer CT.gov Call Center

This is a first-in-human, Phase 1, open label, multicenter, multiple dose, dose escalation and dose expansion study intended to evaluate the safety, pharmacokinetic, pharmacodynamic and potential clinical benefit of PF-07257876, a CD47-PD-L1 bispecific antibody, in participants with selected advanced or metastatic tumors for whom no standard therapy is available. The study contains 2 parts, single agent Dose Escalation (Part 1) to determine the recommended dose of PF-07257876, followed by Dose Expansion (Part 2) in selected tumor types at the recommended dose.

Study to Test the Safety and Tolerability of PF-07257876 in Participants With Selected Advanced Tumors.

A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07257876 IN PATIENTS WITH ADVANCED OR METASTATIC TUMORS

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

DLTs will be evaluated during Cycle 1 (a cycle is 28 days) in Part 1. The number of DLTs will be used to determine the optimal dose

AEs characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 5.0), timing, seriousness, and relationship to study therapy.

Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.

Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Maximum observed plasma concentration of PF-07257876 (Cmax)

Time to maximal observed plasma concentration of PF-07257876 (Tmax)

Area under the concentration-time curve from time zero to the last quantifiable time point prior to the next dose.

Maximum observed steady state plasma concentration of PF-07257876 (Cmax, ss)

Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss).

Area Under the curve within one dose interval at steady state (AUCtau,ss)

Incidence, titers, and duration (if data permit) of antidrug antibodies (ADA) and neutralizing antibodies against PF-07257876

Immune biomarker levels in archival biopsies and/or de novo and on-treatment tumor biopsies.

PD-L1 expression levels in pretreatment tumor biopsies

Tumor response assessment based on RECIST 1.1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety Study of the Drug MM-151 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment	NCT01520389	Advanced Solid ... Colorectal Canc... Squamous Cell H... Non Small Cell ... Triple Negative...	MM-151 MM-151 + irinot...	18 Years -	Merrimack Pharmaceuticals
A Safety Study of MM-121 With Cetuximab and Irinotecan in Patients With Advanced Cancers	NCT01451632	Colorectal Canc... Squamous Cell H... Non-small Cell ... Triple Negative... Other Tumors Wi...	MM-121 Irinotecan Cetuximab	18 Years -	Merrimack Pharmaceuticals
Safety of a Single Administration of AAV2hAQP1, an Adeno-Associated Viral Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in People With Irradiation-Induced Parotid Salivary Hypofunction	NCT02446249	Squamous Cell H... Radiation Induc... Salivary Hypofu...	AAV2hAQP1	18 Years -	MeiraGTx UK II Ltd
Safety Study of the Drug MM-151 in Patients With Advanced Solid Tumors Resisting Ordinary Treatment	NCT01520389	Advanced Solid ... Colorectal Canc... Squamous Cell H... Non Small Cell ... Triple Negative...	MM-151 MM-151 + irinot...	18 Years -	Merrimack Pharmaceuticals
Safety of a Single Administration of AAV2hAQP1, an Adeno-Associated Viral Vector Encoding Human Aquaporin-1 to One Parotid Salivary Gland in People With Irradiation-Induced Parotid Salivary Hypofunction	NCT02446249	Squamous Cell H... Radiation Induc... Salivary Hypofu...	AAV2hAQP1	18 Years -	MeiraGTx UK II Ltd
Study to Test the Safety and Tolerability of PF-07257876 in Participants With Selected Advanced Tumors.	NCT04881045	Non-Small Cell ... Squamous Cell C... Ovarian Cancer	PF-07257876	18 Years -	Pfizer

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