Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.

Participants will be administered with the MTD or RP2D of AMG 994 identified in the dose escalation part of the study, in combination with AMG 404.

Administered as an intravenous (IV) infusion.

AMG 994

AMG 404

The primary objective of this study is to evaluate the safety, tolerability, and maximum tolerated dose (MTD)/maximum tolerated combination dose (MTCD) or recommended phase 2 dose (RP2D) of AMG 994 as monotherapy and AMG 994 in combination with AMG 404 in participants with advanced solid tumors.

AMG 994 will be administered by short term intravenous (IV) infusion once weekly in each 28-day cycle and AMG 404 will be administered by short-term IV infusion once every 4 weeks (Q4W) in a 28 day cycle (on day 1 of cycle 2 and beyond). The study will be conducted in 2 parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.

Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors

A Phase 1, Multicenter, Open-label, Dose Exploration and Dose Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 994 Monotherapy and Combination of AMG 994 and AMG 404 in Subjects With Advanced Solid Tumors

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Amgen

Neoplasms

All Conditions

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Anti-Infective Agents

Vitamins

Amino Acids

Pembrolizumab

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Oxaliplatin

Bevacizumab

Atezolizumab

Carboplatin

Leucovorin

Fluorouracil

Irinotecan

Pemetrexed

Everolimus

Palbociclib

Afatinib

Trametinib

Sotorasib

Panitumumab

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immune Checkpoint Inhibitors

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Immunosuppressive Agents

Immunologic Factors

Tyrosine Kinase Inhibitors

Folinic Acid

Folate

Vitamin B9

Tyrosine

Experimental: Sotorasib + trametinib + panitumumab Dose Exploration and Dose Expansion

* Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
* Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.

Experimental: Sotorasib + RMC-4630 Dose Exploration and Dose Expansion

* Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
* Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants, with KRAS p.G12C mutant advanced solid tumors.

Experimental: Sotorasib + afatinib Dose Exploration and Dose Expansion

* Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer.
* Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.

Experimental: Sotorasib + panitumumab +/- chemotherapy Dose Exploration and Dose Expansion

* Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.
* Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.

Experimental: Sotorasib + atezolizumab Dose Exploration and Dose Expansion

* Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer.
* Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.

Experimental: Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab Dose Exploration and Dose Expansion

* Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer.
* Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.

Experimental: Sotorasib only Dose Exploration and Dose Expansion

* Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer with brain metastases.
* Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer with brain metastases.

Experimental: Sotorasib + palbociclib Dose Exploration and Dose Expansion

* Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor.
* Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.

Experimental: Sotorasib + pembrolizumab Dose Exploration and Dose Expansion

* Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant non small cell lung cancer.
* Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS P.G12C mutant non small cell lung cancer.

Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ chemotherapy Dose Exploration and Dose Expansion

* Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer.
* Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced colorectal cancer.

Experimental: Sotorasib + TNO155 Dose Exploration and Dose Expansion

* Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
* Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.

Experimental: Sotorasib + BI 1701963 Dose Exploration and Dose Expansion

* Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors.
* Upon completion of dose exploration part of the study the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced non-small cell lung cancer and advanced colorectal cancer.

Experimental: Sotorasib + AMG 404 Dose Exploration and Dose Expansion • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors

Experimental: Sotorasib + everolimus Dose Exploration and Dose Expansion • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor. • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.

Sotorasib administered orally as a tablet.

Trametinib administered orally as a tablet.

RMC-4630 administered orally as a capsule.

RMC-4630

afatinib administered orally as a tablet.

pembrolizumab administered as an intravenous (IV) infusion.

Panitumumab administered as an IV infusion.

Carboplatin, pemetrexed, docetaxel administered as an IV infusion.

Carboplatin, pemetrexed, docetaxel, paclitaxel

Atezolizumab administered as an IV injection.

Palbociclib administered orally as a tablet.

MVASI® (bevacizumab-awwb) administered as an IV infusion.

MVASI® (bevacizumab-awwb)

TNO155

Chemotherapy combination of leucovorin administered as an IV injection, 5-fluorouracil (5-FU) administered as IV bolus injection or IV continuous infusion (depending on dose), and irinotecan administered as IV injection.

IV Chemotherapy (Regimen 1)

IV chemotherapy combination of leucovorin administered as an IV injection, 5-FU administered as IV bolus injection or IV continuous infusion (depending on dose), and oxaliplatin administered as IV injection.

IV Chemotherapy (Regimen 2)

BI 1701963

Amgen Call Center

To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid tumors.

Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)

A Phase 1b, Protocol Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Sotorasib Monotherapy and in Combination With Other Anti-cancer Therapies in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Intracranial objective response rate assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM).

Intracranial disease control rate assessed per RANO-BM.

Intracranial duration of response assessed per RANO-BM.

Non-intracranial PFS assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Overall PFS assessed per RECIST 1.1 and RANO-BM.

Blood and Lymph Conditions

Immune System Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Dexamethasone acetate

Blinatumomab

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Blinatumomab will be administered as a continuous intravenous infusion (cIV).

AMG 404 will be administered as an intravenous infusion (IV).

Dexamethasone will be administered orally or intravenously prior to blinatumomab treatment, as needed.

Dexamethasone Premedication

The primary objective of this phase 1b study is to evaluate the safety and tolerability of blinatumomab and AMG 404 in combination in adults with R/R B-ALL and to estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMG 404 when combined with continuous intravenous infusion (cIV) blinatumomab.

Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor ALL

A Phase 1b Open-label Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Administration of Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (ALL)

Investigators determined whether an adverse event (AE) qualified as a DLT per pre-specified protocol defined criteria. An AE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment.

A TEAE was defined as any AE starting on or after first dose of blinatumomab or AMG 404. The investigator used clinical judgment to assess causal relationship. A serious AE (SAE) was defined as any AE that:

* results in death,
* immediately life-threatening,
* requires in-patient hospitalization or prolongation of existing hospitalization,
* results in persistent or significant disability/incapacity,
* is a congenital anomaly/birth defect, and/or
* other medically important serious AE.

AEs of interest (EOIs) for blinatumomab included capillary leak syndrome, cytokine release syndrome, decreased immunoglobulins, elevated liver enzyme, embolic and thrombotic events, immunogenicity, infections, infusion reactions without considering duration, leukoencephalopathy, progressive multifocal leukoencephalopathy, neurologic events, neutropenia and febrile neutropenia, pancreatitis, and tumor lysis syndrome. EOIs for AMG 404 included non-infectious diarrhea and hemorrhages.

Hematological remissions were defined by the following criteria:

CR:

* Less than 5% blasts in the bone marrow (BM)
* No evidence of disease
* Full recovery of peripheral blood (PB) counts:
* Platelets \> 100 000/μl
* Absolute neutrophil count (ANC) \> 1000/μl

CR with only CRh:

* Less than 5% blasts in the BM
* No evidence of disease
* Partial recovery of PB counts:
* Platelets \> 50 000/μl and
* ANC \> 500/μl

Percentage of participants with CR/CRh were summarized along with corresponding 95% exact confidence interval (CI) using the Clopper-Pearson method.

Hematological remissions were defined by the following criteria:

CR:

* Less than 5% blasts in the BM
* No evidence of disease
* Full recovery of PB counts:
* Platelets \> 100 000/μl
* ANC \> 1000/μl

Percentage of participants with CR were summarized along with corresponding 95% exact CI using the Clopper-Pearson method.

Duration of CR was calculated from the date CR was first achieved within the first 2 cycles until the earliest date of disease assessment indicating a relapse event or death due to any cause, whichever occurred first. Months were calculated as days from date of CR to event/censor date, divided by 30.5.

Median time to event and 95% CI was summarized using the Kaplan-Meier (KM) method.

Duration of CR/CRh was calculated from the date CR/CRh was first achieved within the first 2 cycles until the earliest date of disease assessment indicating a relapse event or death due to any cause, whichever occurred first. Months were calculated as days from date of CR/CRh to event/censor date, divided by 30.5.

Median time to event and 95% CI was summarized using the KM method.

Pharmacokinetic (PK) parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.

PK parameters were estimated using standard non-compartmental approaches and summarized by dose level as pre-specified in the protocol.

Only samples testing positive for anti-blinatumomab binding antibodies were to be tested for neutralizing antibodies (NAbs) as pre-specified in the protocol.

Only samples testing positive for anti-AMG 404 binding antibodies were to be tested for NAbs as pre-specified in the protocol.

All-cause mortality was collected for all participants enrolled/randomized in the study. Serious AEs and other AEs were collected for all participants who received at least one dose of study drug.

Blinatumomab cIV was administered at 9 μg/day on Days 1 to 7, then at 28 μg/day thereafter. Each cycle consisted of 42 days and included a 14-day blinatumomab treatment-free interval between Days 29 and 42. The treatment-free interval could be prolonged by up to 7 days if deemed necessary by the investigator. AMG 404 was administered IV at 240 mg, starting on C1D11 and dosed Q4W thereafter. Participants could receive up to 5 cycles.

Cohort 1: Blinatumomab + AMG 404 (240 mg)

Blinatumomab cIV was administered at 9 μg/day on Days 3 to 9, then at 28 μg/day thereafter. Cycle 1 consisted of 44 days and included a 14-day blinatumomab treatment-free interval between Days 31 and 44. Each cycle thereafter consisted of 42 days and included a 14-day blinatumomab treatment-free interval between Days 29 and 42. The treatment-free interval could be prolonged by up to 7 days if deemed necessary by the investigator. AMG 404 was administered IV at 480 mg, starting on C1D1 and dosed Q4W thereafter. Participants could receive up to 5 cycles.

Cohort 2a: Blinatumomab + AMG 404 (480 mg)

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Study Director

DLT Analysis Set: included DLT-evaluable participants in the Safety Analysis Set. A participant was DLT-evaluable if the participant had completed DLT-evaluable period which begins with the first AMG 404 dose and includes 28 days after the second AMG 404 dose is administered or experienced a DLT any time during the DLT-evaluable period.

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

TEAEs

Serious TEAEs

Blinatumomab-related TEAEs

AMG 404-related TEAEs

EOIs

Safety Analysis Set: defined as all participants who were enrolled and received at least 1 dose of blinatumomab and AMG 404.

Number of Participants Who Experienced Treatment-Emergent AEs (TEAEs)

Within the First 2 Cycles

Across All Cycles

Percentage of Participants Who Achieved Complete Remission (CR) or CR With Partial Hematological Recovery (CRh) (CR/CRh)

Percentage of Participants Who Achieved CR

Safety Analysis Set: defined as all participants who were enrolled and received at least 1 dose of blinatumomab and AMG 404. Includes only participants who achieved CR within the first 2 cycles of treatment.

Median Duration of CR in Participants Who Achieved CR Within First 2 Cycles

Safety Analysis Set: defined as all participants who were enrolled and received at least 1 dose of blinatumomab and AMG 404. Includes only participants who achieved CR/CRh within the first 2 cycles of treatment.

Median Duration of CR/CRh in Participants Who Achieved CR/CRh Within First 2 Cycles

Blinatumomab cIV was administered at 9 μg/day on Days 1 to 7. Cycle 1 consisted of 42 days.

Cohort 1; Cycle 1: Blinatumomab 9 μg/Day

Blinatumomab cIV was administered at 28 μg/day on Days 8 to 28. Cycle 1 consisted of 42 days. AMG 404 was administered IV at 240 mg, starting on C1D11 and dosed Q4W thereafter.

Cohort 1; Cycle 1: Blinatumomab 28 μg/Day

Blinatumomab cIV was administered at 28 μg/day. Cycle 2 consisted of 42 days and included a 14-day blinatumomab treatment-free interval between Days 29 and 42. The treatment-free interval could be prolonged by up to 7 days if deemed necessary by the investigator. AMG 404 was administered IV at 240 mg, starting on C1D11 and dosed Q4W thereafter.

Cohort 1; Cycle 2: Blinatumomab 28 μg/Day

Blinatumomab cIV was administered at 9 μg/day on Days 3 to 9. Cycle 1 consisted of 44 days. AMG 404 was administered IV at 480 mg, starting on C1D1 and dosed Q4W thereafter.

Cohort 2a; Cycle 1: Blinatumomab 9 μg/Day

Blinatumomab cIV was administered at 28 μg/day on Days 10 to 30. Cycle 1 consisted of 44 days. AMG 404 was administered IV at 480 mg, starting on C1D1 and dosed Q4W thereafter.

Cohort 2a; Cycle 1: Blinatumomab 28 μg/Day

Blinatumomab cIV was administered at 28 μg/day. Cycle 2 consisted of 42 days and included a 14-day blinatumomab treatment-free interval between Days 29 and 42. The treatment-free interval could be prolonged by up to 7 days if deemed necessary by the investigator. AMG 404 was administered IV at 480 mg, starting on C1D1 and dosed Q4W thereafter.

Cohort 2a; Cycle 2: Blinatumomab 28 μg/Day

PK Analysis Set: Defined as all participants in the Safety Analysis Set who have at least 1 PK sample collected. Includes only participants with available data at each timepoint.

Steady-state Concentrations (Css) of Blinatumomab

AMG 404 was administered IV at 240 mg, starting on C1D11 and dosed Q4W thereafter. Each cycle consisted of 42 days.

Cohort 1: AMG 404 (240 mg)

AMG 404 was administered IV at 480 mg, starting on C1D1 and dosed Q4W thereafter. Cycle 1 consisted of 44 days.

Cohort 2a: AMG 404 (480 mg)

Maximum Observed Concentration (Cmax) of AMG 404

Time to Cmax (Tmax) of AMG 404

Area Under the Plasma Concentration-time Curve From Time 0 to 28 Days Post Infusion (AUC0-28d) of AMG 404

Binding Antibody Positive at Anytime

NAb Positive at Anytime

Safety Analysis Set: defined as all participants who were enrolled and received at least 1 dose of blinatumomab and AMG 404. Includes only participants with available data.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors	NCT04727554	Advanced Solid ...	AMG 994 AMG 404	18 Years - 100 Years	Amgen
Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)	NCT04185883	Advanced Solid ... Kirsten Rat Sar...	Sotorasib Trametinib RMC-4630 Afatinib Pembrolizumab Panitumumab Carboplatin, pe... Atezolizumab Palbociclib MVASI® (bevaciz... TNO155 IV Chemotherapy... IV Chemotherapy... BI 1701963 AMG 404 Everolimus	18 Years - 100 Years	Amgen
Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors	NCT04727554	Advanced Solid ...	AMG 994 AMG 404	18 Years - 100 Years	Amgen
Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor ALL	NCT04524455	Acute Lymphobla...	Blinatumomab AMG 404 Dexamethasone P...	18 Years - 99 Years	Amgen
AMG 757 and AMG 404 in Subjects With Small Cell Lung Cancer (SCLC)	NCT04885998	Small Cell Lung...	Tarlatamab AMG 404	18 Years -	Amgen
AMG 404 in Patients With Advanced Solid Tumors	NCT03853109	Advanced Solid ...	AMG 404	18 Years - 100 Years	Amgen
Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor ALL	NCT04524455	Acute Lymphobla...	Blinatumomab AMG 404 Dexamethasone P...	18 Years - 99 Years	Amgen
Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)	NCT04185883	Advanced Solid ... Kirsten Rat Sar...	Sotorasib Trametinib RMC-4630 Afatinib Pembrolizumab Panitumumab Carboplatin, pe... Atezolizumab Palbociclib MVASI® (bevaciz... TNO155 IV Chemotherapy... IV Chemotherapy... BI 1701963 AMG 404 Everolimus	18 Years - 100 Years	Amgen

Spots Global Cancer Trial Database for amg 404

Every month we try and update this database with for amg 404 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 amg 404

Every month we try and update this database with for amg 404 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 amg 404 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.