Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Osimertinib

Antibodies

Antibodies, Bispecific

Immunoglobulins

Mitogens

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

In Part 1 dose escalation, patients will receive EMB-01 IV once weekly and osimertinib PO QD on days 1-28. The treatment cycle repeats every 28 days in the absence of disease progression or unacceptable toxicity. Dose escalation will continue until the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) is reached, or all planned doses are administered.

In Part 2 dose expansion, patients will receive EMB-01 IV once weekly and osimertinib PO QD on days 1-28 at the recommended phase II dose (RP2D) regimen. The treatment cycle repeats every 28 days in the absence of disease progression or unacceptable toxicity.

EMB-01 is a bispecific antibody against epidermal growth factor receptor (EGFR) and the receptor tyrosine kinase Met (cMET).

EMB-01

Osimertinib is an approved, third-generation EGFR tyrosine kinase inhibitor

Xiaodong Sun, MD

Di Hu

Misako Nagasaka

Julia Kathleen Rotow

Yi-Long Wu

This phase Ib/II trial studies the side effects and best dose of EMB-01 when given together with osimertinib in patients with EGFR-mutant non-small cell lung cancer that has spread to other places in the body (advanced or metastatic) and has progressed on standard treatment. EMB-01 and osimertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth in this type of cancer. EMB-01 in combination with osimertinib may work better in treating patients with EGFR-mutant advanced non-small cell lung cancer.

PRIMARY OBJECTIVES:

I. To evaluate the maximum tolerated dose (MTD) and to establish the recommended phase II dose (RP2D) of EMB-01 given in combination with osimertinib in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). (Phase Ib)

II. To preliminarily assess efficacy and further evaluate the safety and tolerability of EMB-01 plus osimertinib at the RP2D in advanced EGFR-mutant NSCLC patients who progressed on prior EGFR tyrosine kinase inhibitor (TKI) treatment. The primary endpoint is objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (Phase II)

SECONDARY OBJECTIVES:

I. To assess the pharmacokinetics (PK) of EMB-01 and osimertinib.

II. To assess the immunogenicity of EMB-01 and osimertinib.

III. To evaluate preliminary antitumor activity of EMB-01 and osimertinib. (Phase I)

IV. To continue to evaluate the antitumor activity of EMB-01 and osimertinib such as progression free survival, best overall response, duration of response, and clinical benefit rate. (Phase II)

EXPLORATORY OBJECTIVES:

I. To explore the relationships between pharmacokinetics, biomarkers, adverse event profiles, and anticancer activity of EMB-01 combined with osimertinib.

OUTLINE: This is a phase Ib, dose-escalation study of EMB-01 and osimertinib followed by a phase II study.

Patients receive EMB-01 intravenously (IV) weekly. Patients also receive osimertinib orally (PO) once daily (QD) on days 1-28. Treatment cycles repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

After the completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

EMB-01 in Combination With Osimertinib in Patients With EGFR Mutant Lung Cancer

A Phase Ib/II, Open-Label, Multi-Center Study of EMB-01 in Combination With Osimertinib in Patients With Advanced/Metastatic EGFR Mutant Lung Cancer

Adverse events and serious adverse events as assessed by CTCAE v5.0

Objective response rate, measured by RECIST 1.1

Best overall response as assessed by RECIST v1.1

Duration of response as assessed by RECIST v1.1

Clinical benefit rate as assessed by RECIST v1.1

Progression free survival as assessed by RECIST v1.1

Maximum measured plasma concentration of EMB-01

Blood samples will be collected from patients post-treatment for assessment of the presence of anti-drug antibodies and neutralizing antibodies.

Labcorp Corporation of America Holdings, Inc

Shanghai EpimAb Biotherapeutics Co., Ltd.

Micronutrients

Anti-Inflammatory Agents

Antiemetics

Gastrointestinal Agents

Hematinics

Vitamins

Pembrolizumab

Bevacizumab

Carboplatin

Dexamethasone

Pemetrexed

Cisplatin

Dexamethasone acetate

Folic Acid

Vitamin B Complex

Vitamin B 12

Hydroxocobalamin

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Trace Elements

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immune Checkpoint Inhibitors

Folic Acid Antagonists

Folinic Acid

Methylcobalamin

Folate

Vitamin B9

Vitamin B12

Cobalamin

Cyanocobalamin

Participants receive pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m\^2 IV (with vitamin supplementation) PLUS cisplatin 75 mg/m\^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4-6 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m\^2 IV Q3W until progression.

Pembrolizumab was given as 200 milligrams (mg) via intravenous (IV) infusion over 30 minutes on Day 1 of each 21-day cycle.

Bevacizumab was given as 15 mg/kg via intravenous (IV) infusion on Day 1 of each 21-day cycle.

Pemetrexed was given as 500 mg/m\^2 via intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle for 4-6 cycles.

Cisplatin was given as 75 mg/m\^2 via intravenous (IV) infusion (administered approximately 30 minutes after pemetrexed infusion) on Day 1 of each 21-day cycle for 4-6 cycles.

Carboplatin was given as Aare Under the Curve (AUC) 5 (5 mg/mL/min; over 15-60 min) via intravenous (IV) infusion (administered immediately after pemetrexed infusion) on Day 1 of each 21-day cycle for 4-6 cycles.

Orally; at least 5 doses of folic acid must be taken during the 7 days preceding the first dose of pemetrexed, and folic acid dosing must continue during the full course of therapy and for 21 days after the last dose of pemetrexed.

Folic acid 350-1000 μg

Intramuscular injection in the week preceding the first dose of pemetrexed and once every 3 cycles thereafter. Subsequent vitamin B12 injections may be given on the same day as pemetrexed administration.

Vitamin B12 1000 μg

For prophylaxis; orally twice per day (or equivalent). Taken the day before, the day of, and the day after pemetrexed administration.

Dexamethasone 4 mg

Baohui Han, MD,PhD

Baohui Han, MD, PhD

This study is designed to evaluate the efficacy and safety of Pembrolizumab in combination with Bevacizumab and chemotherapy in advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation.

Pembrolizumab Plus Bevacizumab and Chemotherapy for Non-Squamous NSCLC Patients

Pembrolizumab Plus Bevacizumab and Chemotherapy as First-Line Treatment for Advanced or Metastatic Non-Squamous NSCLC Patients With EGFR Exon 20 Insertion Mutation: An Open-Label, Single-Arm, Phase II Trial

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1).

PFS is defined as the time from the first dose of study treatment to the first documented progressive disease (PD) per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on blinded independent central review (BICR), or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesion was also considered PD.

OS was defined as the time from the first dose of study treatment to death due to any cause.

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from the first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented.

An AE was defined as any untoward medical occurrence in a participant-administered study treatment that did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented.

The number of participants who discontinued any randomized study drug due to an AE is presented.

Merck Sharp & Dohme LLC

Shanghai Chest Hospital

Professor

Participants will receive IV infusion of HS-20117 once during cycle 1 and once every 2 weeks during subsequent cycles (The duration of each treatment cycle is 28 days)

Phase Ia: patients will receive HS-20117 starting at 400 mg, and subsequent cohorts will test escalating doses, if tolerated, until a maximum tolerated dose (MTD) or maximum applicable dose (MAD) is defined.

Phase Ib: patients will receive HS-20117 at MED or MAD

HS-20117

Peng Zhou

Lin Jiang

Dingzhi Huang, Dr.

Dingzhi Huang

HS-20117 is a fully-human EGFR-MET immunoglobulin G1(IgG1)-like bispecific antibody. The purpose of study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of HS-20117 as a monotherapy for participants with advanced solid tumors.

This is a multicenter, open-label, Phase I clinical study of HS-20117 to evaluate the safety, tolerability, PK, immunogenicity and efficacy in participants with advanced solid tumors. The study consists of phase Ia (dose escalation) and phase Ib (dose expansion). The dose-escalation study will be performed to evaluate the safety, tolerability, PK profile, immunogenicity, and efficacy of HS-20117 in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The subsequent dose-expansion study will be performed to evaluate the efficacy of HS-20117 in participants with locally advanced or metastatic NSCLC who have progressed after prior platinum-based chemotherapy or are intolerant to platinum-based chemotherapy with EGFR exon 20 insertion mutations, and to explore the efficacy of HS-20117 in participants with other advanced solid tumors.

A Phase I Clinical Study of HS-20117 in Participants With Advanced Solid Tumors

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HS-20117 in Participants With Advanced Solid Tumors

MTD is defined as the previous dose level at which 2 or more out of 2-6 subjects experienced a DLT.

MAD is defined as follows: a) based on PK data, it is anticipated that at this dose level, the dose-exposure plateau has been reached, b) based on existing safety data, it is judged that dose escalation following this dose level will have a large safety risk or subject intolerance, or c) based on the PK-PD model, it suggested that the optimal target concentration of safety and efficacy has been explored.

ORR is defined as the percentage of participants with BOR of confirmed CR or confirmed PR per RECIST v1.1

Adverse event (assessed according to NCI CTCAE v5.0) is defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

The Cmax is the maximum observed serum concentration of HS-20117.

Ctrough is the observed serum concentration immediately prior to the next administration.

The Tmax is defined as time to reach maximum observed serum concentration of HS-20117.

The AUCtau is defined as the area under the serum concentration-time curve during a dose interval time period (tau).

The t1/2 is defined as the time it takes for the concentration levels to fall to 50% of their value.

ORR is defined as the percentage of participants with BOR of confirmed CR or confirmed PR per RECIST v1.1.

DCR is deﬁned as the percentage of patients who have a best overall response (confirmed CR, PR, or stable disease for at least 6 weeks) per RECIST v1.1.

DoR only applies to participants whose best overall response is CR or PR based on assessment per RECIST v1.1. The start date is the date of first documented response of CR or PR (i.e. the start date of observed response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying disease.

PFS is defined as the time from the date of randomization or first dose (if randomization is not needed) to the date of the first documented progression or death due to any cause. PFS will be assessed per RECIST v1.1.

OS is defined as the time from the date of randomization or first dose (if randomization is not needed) to the date of death due to any cause. For each participant who is not known to have died as of the cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.

Immunogenicity will be measured by the number of participants that are ADA positive.

Hansoh BioMedical R&D Company

Etoposide

Durvalumab

Etoposide phosphate

Alectinib

Gefitinib

Necitumumab

The patients in this group will receive osimertinib taken in combination with savolitinib

The patients in this group will receive osimertinib taken in combination with gefitinib

The patients in this group will receive osimertinib taken in combination with necitumumab

The patients in this group will receive platinum-containing doublet (carboplatin + pemetrexed) taken in combination with durvalumab.

Patients in this group will not receive study treatment but receive further anticancer care (Standard of Care therapy or other experimental therapies) or supportive care, as clinically indicated, in accordance with local practice.

With Group C, the aim is to understand the clinical course and/or outcome for the overall clinical population after progression on first-line monotherapy with osimertinib.

The patients in this group will receive osimertinib taken in combination with alectinib

The patients in this group will receive osimertinib taken in combination with selpercatinib

The patients in this group will receive platinum-containing doublet (etoposide + carboplatin or cisplatin) taken in combination with durvalumab.

The patients in this group will receive Osimertinib plus platinum-containing doublet (pemetrexed + carboplatin or cisplatin).

The patients in this group will receive osimertinib taken in combination with selumetinib

The patients in this group will receive osimertinib taken in combination with datopotamab deruxtecan.

Osimertinib given orally at 80 mg once daily

Savolitinib will be given orally at 300 mg or 600mg once daily

Savolitinib

Gefitinib given orally at 250 mg once daily

Necitumumab given IV at 800 mg on Day 1 and Day 8 of every 3-week cycle

Durvalumab given IV at 1500 mg on Day 1 of every cycle

Carboplatin given IV on Day 1 of every 21-day cycle for up to 6 cycles

Pemetrexed given IV at 500 mg/m2 body BSA on Day 1 of every cycle

Alectinib given orally at 600mg twice daily and for Japanese patients at 300mg twice daily.

Selpercatinib given orally at 160mg twice daily

Selpercatinib

Selumetinib given orally at 75 mg twice daily for 4 days, followed by 3 days off treatment

Selumetinib

Etoposide 80-100 mg/m2 given IV on day 1, 2 and 3 of every 21-day cycle for up to 4 cycles.

Cisplatin 75-80 mg/m2 given IV on days 1 of each cycle

Datopotamab deruxtecan given IV at 4 or 6 mg/kg on Day 1 of every 3-week cycle.

Datopotamab deruxtecan

Helena A Yu, MD

Phase 2 Platform Study in Patients with Advanced Non-Small Lung Cancer who progressed on First-Line Osimertinib Therapy. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.

This is an open-label, multicentre, multi-drug, biomarker-directed Phase 2 platform study in patients with advanced non-small cell lung cancer (NSCLC) harbouring an epidermal growth factor receptor (EGFR)-sensitizing mutation whose disease has progressed on first-line monotherapy with osimertinib.Treatment options for these patients are limited. Novel treatments for these patients are urgently required.

This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments.

Phase 2 platform study in patients with advanced Non-Small Lung Cancer harbouring an epidermal growth factor receptor (EGFR)-sensitizing mutation with evidence of radiological progression following first-Line osimertinib therapy. This study is modular in design, allowing evaluation of the efficacy, safety and tolerability of multiple study treatments. The study will be conducted in three groups (Groups A, B and C). Patient allocation to a study treatment within each group will be based on tumour molecular profile. Biomarker positive patients or patients with histologically identifiable neuroendocrine transformation to small cell lung cancer (SCLC) or large cell neuroendocrine carcinoma (NEC) will be allocated to a biomarker-matched study treatment in Group A, patients without a biomarker will be allocated to a study treatment in Group B and patients with a biomarker amenable to therapies not currently available in ORCHARD will be allocated to Group C.

Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)

A Biomarker-directed Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Whose Disease Has Progressed on First-Line Osimertinib Therapy.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

The percentage of patients with a confirmed investigator-assessed complete or partial response according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1. Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond progression).

The time from first dose until the date of objective disease progression or death (by any cause in the absence of progression). Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST (Response Evaluation Criteria In Solid Tumours)1.1 defined disease progression or cessation of study treatment (if treating beyond progression).

The time from the date of first response until date of disease progression or death in the absence of disease progression. Patients will be followed up every 6 weeks (±1 week) for the first 24 weeks and every 9 weeks thereafter until RECIST 1.1 defined disease progression or cessation of study treatment (if treating beyond progression).

The time from the date of the first dose of study treatment until death due to any cause.

Blood samples will be collected at various timepoints to evaluate the sparse pharmacokinetics of study therapeutic agents.

Blood samples will be collected at various timepoints to evaluate the serial pharmacokinetics of study therapeutic agents

To evaluate safety and tolerability of each study treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
EMB-01 in Combination With Osimertinib in Patients With EGFR Mutant Lung Cancer	NCT05498389	Metastatic Lung... Advanced Lung N... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ... Stage III Lung ... Stage IIIA Lung... Stage IIIB Lung... EGFR Mutation-R...	EMB-01 Osimertinib	18 Years -	Shanghai EpimAb Biotherapeutics Co., Ltd.
Pembrolizumab Plus Bevacizumab and Chemotherapy for Non-Squamous NSCLC Patients	NCT05751187	Non-squamous NS...	Pembrolizumab Bevacizumab Pemetrexed Cisplatin Carboplatin Folic acid 350-... Vitamin B12 100... Dexamethasone 4...	18 Years - 75 Years	Shanghai Chest Hospital
Pembrolizumab Plus Bevacizumab and Chemotherapy for Non-Squamous NSCLC Patients	NCT05751187	Non-squamous NS...	Pembrolizumab Bevacizumab Pemetrexed Cisplatin Carboplatin Folic acid 350-... Vitamin B12 100... Dexamethasone 4...	18 Years - 75 Years	Shanghai Chest Hospital
A Phase I Clinical Study of HS-20117 in Participants With Advanced Solid Tumors	NCT05940116	Non-Small Cell ... Solid Tumor	HS-20117	18 Years - 75 Years	Hansoh BioMedical R&D Company
Pembrolizumab Plus Bevacizumab and Chemotherapy for Non-Squamous NSCLC Patients	NCT05751187	Non-squamous NS...	Pembrolizumab Bevacizumab Pemetrexed Cisplatin Carboplatin Folic acid 350-... Vitamin B12 100... Dexamethasone 4...	18 Years - 75 Years	Shanghai Chest Hospital
EMB-01 in Combination With Osimertinib in Patients With EGFR Mutant Lung Cancer	NCT05498389	Metastatic Lung... Advanced Lung N... Stage IV Lung C... Stage IVA Lung ... Stage IVB Lung ... Stage III Lung ... Stage IIIA Lung... Stage IIIB Lung... EGFR Mutation-R...	EMB-01 Osimertinib	18 Years -	Shanghai EpimAb Biotherapeutics Co., Ltd.
A Phase I Clinical Study of HS-20117 in Participants With Advanced Solid Tumors	NCT05940116	Non-Small Cell ... Solid Tumor	HS-20117	18 Years - 75 Years	Hansoh BioMedical R&D Company
Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Who Progressed on First-Line Osimertinib Therapy (ORCHARD)	NCT03944772	Non-Small Cell ...	Osimertinib Savolitinib Gefitinib Necitumumab Durvalumab Carboplatin Pemetrexed Alectinib Selpercatinib Selumetinib Etoposide Cisplatin Datopotamab der...	18 Years - 130 Years	AstraZeneca

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