Neoplasms

All Conditions

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Paclitaxel

Everolimus

Albumin-Bound Paclitaxel

MM-141

Chrystal Louis, MD, MPH

This study is a Phase 1 and pharmacologic open-labeled dose-escalation trial using a "3+3" design, evaluating MM-141 at varying dose levels and frequencies.

A Phase 1 Study of MM-141 in Patients With Advanced Solid Tumors

Determine the Phase II dose based either on the maximum tolerated dose (MTD) or recommended dose in patients with advanced solid malignancies.

Merrimack Pharmaceuticals

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Pancreatic Neoplasms

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Pancreatic Cancer

Docetaxel

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Participants with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) harboring NRG1 gene fusions

Participants with non-small cell lung cancer (NSCLC) harboring NRG1 gene fusions

Participants with other solid tumors harboring NRG1 gene fusions

Participants with solid tumors harboring selected HER3 extracellular mutations

HMBD-001 is a humanized IgG1 anti-HER3 monoclonal antibody (mAb). It is administered IV weekly

HMBD-001

Docetaxel 75 mg/m\^2 IV once every 3 weeks

Nab-paclitaxel 125 mg/m\^2 IV on days 1, 8, 15, every 4 weeks

Nab-paclitaxel

Gemcitabine 1000 mg/m\^2 IV on days 1, 8, 15, every 4 weeks

Kon Yew Kwek, BMBCh, DPhil

Nick Pavlakis

Vladimir Andelkovic

Ganessan Kichenadasse

Gary Richardson

Michael Millward

This is a phase 1b multi-center, open-label study of HMBD-001 with or without chemotherapy in participants with advanced solid tumors harboring NRG1 gene fusions or selected HER3 mutations.

Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation

A Phase 1b Study to Evaluate HMBD-001 With or Without Chemotherapy in Participants With Advanced Solid Tumors Harboring NRG1 Gene Fusions or Selected HER3 Mutations

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered to be related to the study treatment.

DLTs will be assessed during the safety run-in phase and are defined as toxicities that meet pre-defined severity criteria and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle (4 weeks for Arm A, 3 weeks for Arm B) of treatment

The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1

Hummingbird Bioscience

Micronutrients

Hematinics

Vitamins

Carboplatin

Pemetrexed

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

escalating doses of MM-121 and gemcitabine on Day 1 and Day 8 of every 3 week cycle

carboplatin at AUC 6 with escalating doses of MM-121 on Day 1 of every 3 week cycle

pemetrexed at 500 mg/m2 with escalating doses of MM-121 on Day 1 of every 3 week cycle

escalating doses of MM-121 and cabazitaxel on Day 1 of every 3 week cycle

MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV

MM-121

Cabazitaxel

administered IV at 1000 mg/m2 or 1250 mg/m2

Victor Moyo, MD

To evaluate the safety and tolerability of escalating doses of MM-121 + certain anticancer therapies

This study was a Phase 1 and pharmacologic dose-escalation trial of MM-121 in combination with certain anticancer therapies. The dose-escalation portion of the study employed a 3 + 3 design to assess the safety, tolerability, and pharmacokinetics of MM-121 administered weekly in combination with certain anticancer therapies in patients with advanced/recurrent cancer. Doses of MM-121 and/or the anticancer therapy were escalated until either the MTD is identified or the combination was shown to be tolerable at the highest planned doses.

Safety Study of MM-121 in Combination With Multiple Anticancer Therapies in Patients With Advanced Solid Tumors

A Phase 1, Pharmacologic and Pharmacodynamic Study of MM-121 in Combination With Multiple Anticancer Therapies in Patients With Advanced Solid Tumors

Safety and tolerability data presented in detail in the adverse events and serious adverse events section of the results posting

Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.

Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8 Pemetrexed doses tested: 500 mg/m2 Day 1 Carboplatin doses tested: 5 or 6 AUC Day 1 Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3

Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.

Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8

Maximum Tolerated Dose reported in Target AUC, as calculated by the Calvert Formula

Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.

Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Carboplatin doses tested: 5 or 6 AUC Day 1

Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.

Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Pemetrexed doses tested: 500 mg/m2 Day 1

Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.

Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3

To establish the safety of escalating doses of MM-121 administered in combination with multiple anti-cancer therapies 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 to be used for the expansion cohort. DLTs were not measured in the Expansion Cohort.

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 cycle 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).

Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle 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

escalating doses of MM-121 and gemcitabine on Day 1 and Day 8 of every 3 week cycle

MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV

MM-121 Plus Gemcitabine

carboplatin at AUC 6 with escalating doses of MM-121 on Day 1 of every 3 week cycle

MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV

Carboplatin: administered at AUC 6

MM-121 Plus Carboplatin

pemetrexed at 500 mg/m2 with escalating doses of MM-121 on Day 1 of every 3 week cycle

MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV

Pemetrexed: administered IV at 500 mg/m2

MM-121 Plus Pemetrexed

escalating doses of MM-121 and cabazitaxel on Day 1 of every 3 week cycle

MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV

Cabazitaxel: administered IV at 20 mg/m2 or 25 mg/m2

MM-121 Plus Cabazitaxel

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

France

Region of Enrollment

Clinical Trial Manager

MM-121 20 mg/kg one-time loading dose on Cycle 1, Week 1 followed 12 mg/kg IV maintenance doses weekly for 3-week cycles

gemcitabine 1000 mg/m2 IV on Days 1 and 8 of each 3-week cycle

MM-121 Plus Gemcitabine: Cohort 1

MM-121 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance doses weekly for each 3-week cycle

Gemcitabine: 1000 mg/m2 IV on Day 1 And Day 8 of each 3-week cycle

MM-121 Plus Gemcitabine: Cohort 2

MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance doses weekly for each 3-week cycle

Carboplatin at AUC 6 Day 1 of every 3 week cycle

MM-121 Plus Carboplatin: Cohort 1

MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance doses weekly for each 3-week cycle

Carboplatin at AUC 5 Day 1 of every 3 week cycle

MM-121 Plus Carboplatin: Cohort 2

MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance doses weekly for each 3-week cycle

Carboplatin at AUC 5 Day 1 of every 3 week cycle

MM-121 Plus Carboplatin: Cohort 3

MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12 mg/kg IV maintenance dose weekly for every 3-week cycle

Pemetrexed at 500 mg/m2 IV on Day 1 of every 3 week cycle

MM-121 Plus Pemetrexed: Cohort 1

MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg IV maintenance dose weekly for every 3-week cycle

Pemetrexed at 500 mg/m2 IV on Day 1 of every 3 week cycle

MM-121 Plus Pemetrexed: Cohort 2

MM-121: 20 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 12mg/kg IV maintenance doses weekly for each 3-week cycle

Cabazitaxel: 20 mg/m2 IV on Day 1 of each 3-week cycle

MM-121 Plus Cabazitaxel: Cohort 1

MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg maintenance doses weekly for each 3-week cycle

Cabazitaxel: 20 mg/m2 IV on Day 1 of each 3-week cycle

MM-121 Plus Cabazitaxel: Cohort 2

MM-121: 40 mg/kg IV one-time loading dose on Cycle 1, Week 1 followed by 20 mg/kg maintenance doses weekly for each 3-week cycle

Cabazitaxel: 25 mg/m2 IV on Day 1 of each 3-week cycle

MM-121 Plus Cabazitaxel: Cohort 3

To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Anticancer Therapies

one-time loading dose

maintenance dose

escalating doses of MM-121 and gemcitabine on Day 1 and Day 8 of every 3 week cycle

MM-121: MM-121 administered at 20 mg/kg IV loading dose followed by12mg/kg/week IV or 40 mg/kg IV loading dose followed by 20mg/kg/week IV

Gemcitabine: administered IV at 1000 mg/m2 or 1250 mg/m2

Note: data provided below is for MM-121 doses only for the combination. Combination therapy MTDs are provided in separate endpoint measures.

To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: MM-121 Doses

MM-121 + Gemcitabine

NOTE: Maximum tolerated dose is for the combination of gemcitabine and MM-121. MTD of MM-121 is provided in separate endpoint.

To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Gemcitabine

MTD of the MM-121 + Carboplatin combination NOTE: MTD of MM-121 for this combination provided in separate endpoint

MM-121 + Carboplatin

To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Carboplatin

MTD of combination of MM-121 + Pemetrexed - NOTE: MTD of MM-121 for this combination provided in separate endpoint

MM-121 + Pemetrexed

To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Pemetrexed

MTD of MM-121 + Cabazitaxel combination - NOTE: MTD of MM-121 for this combination provided in separate endpoint

MM-121 + Cabazitaxel

To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Cabazitaxel

To Characterize Dose-limiting Toxicities (DLTs) Associated With the Combination of MM-121 With Anticancer Therapies

Objective Response Rate

MM-121 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose plus gemcitabine 1000mg/m² or 1250mg/m²

MM-121 + Gemcitabine: 20/12 mg/kg

MM-121 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose Plus carboplatin AUC 6

MM-121 + Carboplatin: 20/12 mg/kg

MM-121 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose Plus pemetrexed 500 mg/m²

MM-121 + Pemetrexed: 20/12 mg/kg

MM-121 20 mg/kg loading dose followed by 12 mg/kg weekly maintenance dose Plus Cisplatin 20 mg/m2 or 25 mg/m2

MM-121 + Cisplatin: 20/12 mg/kg

MM-121 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose plus gemcitabine 1000mg/m² or 1250mg/m²

MM-121 + Gemcitabine: 40/20 mg/kg

MM-121 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose Plus carboplatin AUC 6

MM-121 + Carboplatin: 40/20 mg/kg

MM-121 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose Plus pemetrexed 500 mg/m²

MM-121 + Pemetrexed: 40/20 mg/kg

MM-121 40 mg/kg loading dose followed by 20 mg/kg weekly maintenance dose Plus Cisplatin 25 mg/m2

MM-121 + Cisplatin: 40/20 mg/kg

Pharmacokinetics

Pharmacokinetics (AUClast)

Immunogenicity

Overall Study

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Cetuximab

Immunoglobulin G

Mitogens

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

All participants receive HMBD-001 with docetaxel

All participants receive HMBD-001 with docetaxel plus cetuximab

HMBD-001 is a humanized Immunoglobulin G1 (IgG1) anti-Human Epidermal Growth Factor Receptor 3(HER3) monoclonal antibody (mAb). It is administered intravenously (IV) weekly

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

Vinod Ganju

Vinod Prof Ganju

Samantha Bowyer

Aaron Tan

Jens Samol

This is a phase 1b multi-center, open-label study of HMBD-001 in combination with docetaxel with or without cetuximab in participants with locally advanced or metastatic squamous Non-Small Cell Lung Cancers

Study of an Anti-HER3 Antibody, HMBD-001, With Docetaxel +/- Cetuximab in Advanced Squamous Non-small Cell Lung Cancers

A Phase 1b Study to Evaluate HMBD-001 in Combination With Docetaxel With or Without Cetuximab in Participants With Advanced Squamous Non-small Cell Lung Cancers

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered to be related to the study treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1 Study of MM-141 in Patients With Advanced Solid Tumors	NCT01733004	Hepatocellular ...	MM-141	18 Years -	Merrimack Pharmaceuticals
Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation	NCT05919537	Non-Small Cell ... Pancreatic Canc... Locally Advance... Metastatic Soli...	HMBD-001 Docetaxel Nab-paclitaxel Gemcitabine	18 Years -	Hummingbird Bioscience
Safety Study of MM-121 in Combination With Multiple Anticancer Therapies in Patients With Advanced Solid Tumors	NCT01447225	Solid Tumors	MM-121 Carboplatin Pemetrexed Cabazitaxel Gemcitabine	18 Years -	Merrimack Pharmaceuticals
Study of an Anti-HER3 Antibody, HMBD-001, With Docetaxel +/- Cetuximab in Advanced Squamous Non-small Cell Lung Cancers	NCT05910827	Advanced or Met...	HMBD-001 Docetaxel Cetuximab	18 Years -	Hummingbird Bioscience
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
A Phase 1 Study of MM-141 in Patients With Advanced Solid Tumors	NCT01733004	Hepatocellular ...	MM-141	18 Years -	Merrimack Pharmaceuticals
A Phase 1 Study of MM-141 in Patients With Advanced Solid Tumors	NCT01733004	Hepatocellular ...	MM-141	18 Years -	Merrimack Pharmaceuticals
Phase 1 Combination Study of MM-151 With MM-121, MM-141, or Trametinib	NCT02538627	Colorectal Canc... Non-small Cell ... Squamous Cell C...	MM-151 MM-121 MM-141 trametinib	18 Years -	Merrimack Pharmaceuticals
Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation	NCT05919537	Non-Small Cell ... Pancreatic Canc... Locally Advance... Metastatic Soli...	HMBD-001 Docetaxel Nab-paclitaxel Gemcitabine	18 Years -	Hummingbird Bioscience

Spots Global Cancer Trial Database for erbb3

Every month we try and update this database with for erbb3 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for erbb3

Every month we try and update this database with for erbb3 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for erbb3 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.