Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Rare Diseases

Small Cell Lung Carcinoma

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

AZD2811 200mg IV QD CnD1 \& D4 every 4weeks

AZD2811

This study is a single arm, multi-center phase II study of AZD 2811 monotherapy in patients with relapsed small cell lung cancer (SCLC) as a second or third line therapy.

Patients will continue to receive study treatment as described above, until they demonstrate objective disease progression (determined by RECIST 1.1) or they meet any other discontinuation criteria.

AZD 2811 Monotherapy in Relapsed Small Cell Lung Cancer Patients [SUKSES-N3]

Phase II, Single-arm Study of AZD 2811 Monotherapy in Relapsed Small Cell Lung Cancer Patients [SUKSES-N3]

Assessments to be performed using CT or MRI scans. To be measured

AstraZeneca

Samsung Medical Center

Principal Investigator

Blood and Lymph Conditions

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Cytarabine

Venetoclax

Azacitidine

Decitabine

Pyrazole

Antimetabolites

Enzyme Inhibitors

Participants with AML will receive intevenous (IV) infusion of AZD2811 Dose 1 on Days 1 and 4 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.

Participants with AML and myelodysplastic syndrome (MDS) will receive IV infusion of AZD2811 Dose 2 on Days 1 and 4 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.

Participants with AML and MDS will receive IV infusion of AZD2811 Dose 3 on Days 1 and 4 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.

Participants with AML and MDS will receive IV infusion of AZD2811 Dose 4 on Days 1 and 4 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.

Participants with AML will receive IV infusion of AZD2811 Dose 5 on Days 1 and 4 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.

Participants with AML will receive IV infusion of AZD2811 Dose 2 on Days 1, 4, 15, and 18 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.

Participants with AML will receive IV infusion of AZD2811 Dose 6 on Days 1, 4, 15, and 18 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.

Participants with AML and MDS will receive Azacitidine 75 mg/m\^2 of body surface area (BSA) by subcutaneous (SC) injection or IV infusion prior to the start of AZD2811 infusion on Days 1 through 7 or for 5 consecutive weekdays (Days 1 through 5) with treatment holidays on the 2 weekend days (Days 6 and 7), and the remaining azacitidine dosing will be administered on the first 2 weekdays of the 2nd week (Days 8 and 9) of each 28-day cycle. Participants will receive IV infusion of AZD2811 Dose 3 on Days 1 and 4 of each 28-day cycle. Participants will receive the study treatment until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.

Participants with AML will receive Azacitidine 75 mg/m\^2 of BSA by SC injection or IV infusion prior to the start of AZD2811 infusion on Days 1 through 7 or for 5 consecutive weekdays (Days 1 through 5) with treatment holidays on the 2 weekend days (Days 6 and 7), and the remaining azacitidine dosing will be administered on the first 2 weekdays of the 2nd week (Days 8 and 9) of each 28-day cycle. Participants will receive IV infusion of AZD2811 Dose 4 on Days 1 and 4 of each 28-day cycle. Participants will receive the treatment until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.

Participants with AML will receive Azacitidine 75 mg/m\^2 of BSA by SC injection or IV infusion prior to the start of AZD2811 infusion on Days 1 through 7 or for 5 consecutive weekdays (Days 1 through 5) with treatment holidays on the 2 weekend days (Days 6 and 7), and the remaining azacitidine dosing will be administered on the first 2 weekdays of the 2nd week (Days 8 and 9) of each 28-day cycle. Participants will receive IV infusion of AZD2811 Dose 2 on Days 1, 4, 15, and 18 of each 28-day cycle. Participants will receive the treatment until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.

Participants with AML will receive Azacitidine 75 mg/m\^2 of BSA by SC injection or IV infusion prior to the start of AZD2811 infusion on Days 1 through 7 or for 5 consecutive weekdays (Days 1 through 5) with treatment holidays on the 2 weekend days (Days 6 and 7), and the remaining azacitidine dosing will be administered on the first 2 weekdays of the 2nd week (Days 8 and 9) of each 28-day cycle. Participants will receive IV infusion of AZD2811 Dose 6 on Days 1, 4, 15, and 18 of each 28-day cycle. Participants will receive the treatment until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.

Participants with AML will receive IV infusion of AZD2811 Dose 2 on Days 1 and 4 of each 28-day cycle and venetoclax 100 mg orally (PO) on Day 1 and 200 mg PO from Days 2 to 28 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.

Participants with AML will receive IV infusion of AZD2811 Dose 2 on Days 1 and 4 of each 28-day cycle and venetoclax 100 mg orally (PO) on Day 1, 200 mg PO on Day 2, and 400 mg PO from Days 3 to 28 of each 28-day cycle until disease progression, unacceptable toxicity, or the decision to discontinue treatment by the participant or the study physician, whichever occurs first.

AZD2811 will be administered by IV infusion with the specified dose level as reported in arms in 28-day cycles.

Azacitidine is supplied in vials of 25 mg/mL powder for suspension for injection. After reconstitution, each vial contains a maximum of 100 mg. Participants should be pre-medicated for nausea and vomiting according to institutional standards before receiving azacitidine. Participants will receive 75 mg/m² on Days 1 through 7 or for 5 consecutive weekdays with rest on the 2 weekend days, and azacitidine dosing the first 2 weekdays of the next week of each 28-day cycle.

Venetoclax (VENCLEXTA®) is approved by the FDA for use in combination with azacitidine, or decitabine, or low-dose cytarabine for the treatment of newly-diagnosed AML in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. Venetoclax is planned to be given at a dose of 100 mg orally (PO) on Day 1 and 200 mg (PO) on Days 2- 28 of each 28-day cycle or 100 mg orally (PO) on Day 1, 200 mg PO on Day 2, and 400 mg PO from Days 3 to 28 of each 28-day cycle. The third participant in Group 3 Arm A will only be enrolled after the first 2 participants will receive ≥2 weeks of treatment and have shown no evidence of toxicity observed to be compatible with a DLT.

Howard Burris, MD

This is a Phase I/II clinical study to determine the maximum tolerated dose (MTD), and schedule, safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD2811 monotherapy or with combination agent(s) in relapsed/refractory acute myeloid leukaemia (AML) participants or treatment-naïve AML participants not eligible for intensive induction therapy. In addition, the study will explore the potential clinical activity by assessing anti-tumour activity in participants. The study was terminated early as a result of AstraZeneca's strategic review across the AZD2811 programme. Part A data were collected for initial cohorts; the MTD/recommended Phase 2 dose (RP2D) dose and schedule of AZD2811 monotherapy or with combination agents were not determined. Part B of the study was not initiated

This is a Phase I/II clinical study to determine the MTD and schedule, safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD2811 monotherapy or with combination agent(s) in relapsed/refractory AML participants or treatment-naïve AML participants not eligible for intensive induction therapy. The study will also explore the potential clinical activity by assessing anti-tumour activity in participants. The study will be conducted in two parts, designated Part A, dose escalation, and Part B, dose expansion. Participants will be enrolled in either Part A or Part B according to the Investigator's judgment of the most appropriate treatment for the individual participant and slot availability.

Part A - Dose Escalation

Approximately 48 evaluable treatment-naïve AML participants not eligible for intensive induction therapy or relapsed/refractory AML participants will be enrolled in Arm 1 and Arm 2 of the monotherapy escalation in Part A of this study.

The dose escalation and de-escalation plan for evaluating AZD2811 will follow the Bayesian Adaptive Design scheme which combines prior expectations about the dose toxicity relationship and applies the data at the end of each cohort to recommend a dose and schedule for the next cohort. The total number of participants will depend upon the number of dose escalations, de-escalations, and schedule changes necessary. At least 3 and up to 6 evaluable participants will be required for each dose cohort.

Part A Group 1, Arm A - Day 1 and 4 Monotherapy Dose Escalation:

Participants will receive a single 2- or 4- hour IV infusion on Day 1 and Day 4 of each 28-day cycle. Dosing frequency and schedule may be adjusted during the study on the basis of emerging safety and pharmacokinetic data. Approximately 22 participants will be enrolled.

Part A Group 1, Arm B - Day 1, 4, 15, and 18 Monotherapy Dose Escalation:

A Day 1, 4, 15, and 18 every 4 weeks or 28 days (Q4W) schedule will be investigated in addition to the Day 1 and 4 Q4W schedule. The proposed starting dose for this schedule is 300 mg/infusion AZD2811 on Day 1, 4, 15 and 18 (i.e. cumulative dose 1200 mg/Q4W). This starting dose is less than daily doses shown to be tolerated in the AML setting, and the cumulative cycle dose/Q4W does not exceed the highest dose shown to be tolerated (600 mg/infusion Day 1, 4 cumulative 1200 mg Q4W). Approximately 18 participants will be enrolled.

Combination Escalation:

AZD2811 can be escalated (in the combination setting) independent of the monotherapy dose explored, after thorough examination of the available safety data. The combination therapy exploration will not impact the dose to be further explored in the monotherapy setting nor will the monotherapy impact the dose in the combination setting. As such, the number of cohorts in the monotherapy setting can differ from the number of cohorts in the combination setting. The safety observations of the monotherapy will be considered by the Safety Review Committee (SRC) in the overall decision-making process for subsequent dose exploration decision.

A rolling 6 design will be applied to both of the AZD2811 and combination arms. The rolling 6 method allows accrual of 3 to 6 participants concurrently onto a dose level based on the numbers of participants who are currently enrolled and evaluable, who experience a dose-limiting toxicity (DLT), and who remain at risk of developing a DLT.

Part A Group 2 Arm A - Day 1 and 4 Azacitidine Combination Escalation:

A starting dose of 400 mg of AZD2811 will be used for investigation in combination with the standard dose of the hypomethylating agent (HMA) azacitidine. In this dose escalation part, approximately 12-15 evaluable treatment-naïve AML participants not eligible for intensive induction therapy or relapsed/refractory AML will be enrolled and dosed in ascending doses of AZD2811 and standard dose of azacitidine at 75 mg/m² of body surface area subcutaneously (SC) in all territories or optionally/alternatively by IV in the United States (US) as per national prescribing information.

Part A Group 2 Arm B - Day 1, 4, 15, and 18 Azacitidine Combination Dose Escalation

In order to increase dose intensity during the 4 week cycle, and improve efficacy in the combination setting, AZD2811 will also be explored on the Days 1, 4, 15 and 18 schedule in the azacitidine combination and start at a lower daily dosage that has been shown to be safe while administered every 28 days. The proposed starting dose for this schedule is 300 mg/infusion AZD2811 on Day 1, 4, 15 and 18 (i.e., cumulative dose per 28 days is 1200 mg/Q4W) and standard dose and use of azacitidine 75 mg/m² of body surface area SC in all territories or optionally/alternatively by IV in the US as per national prescribing information. Approximately 18 participants will be enrolled.

Venetoclax Combination:

Approximately 18-21 evaluable relapsed/refractory AML participants will be enrolled and dosed with AZD2811 and venetoclax. In cohort 1v, AZD2811 will be administered at 200 mg IV on Days 1 and 4 every 28 days (Q4W) and venetoclax will be given 100 mg orally (PO) on Day 1 and 200 mg (PO) with a meal and water on Days 2- 28 for the 1st cycle. The third participant in cohort 1 (AZD2811 at 200 mg) will only be enrolled after the first 2 participants have received ≥ 2 weeks of treatment and have shown no evidence of toxicity observed to be compatible with a DLT, and further dose escalations of AZD2811 will occur at the discretion of the SRC.

The dose of AZD2811 can be escalated (in the combination setting) independent of the monotherapy dose explored, after thorough examination of the available safety data of the current and the previous cohorts. The combination therapy exploration will not impact the dose further explored in the monotherapy setting nor will the monotherapy impact the dose in the combination setting. As such, the number of cohorts in the monotherapy setting can differ from the number of cohorts in the combination setting. The safety observations of the monotherapy will be considered by the SRC in the overall decision-making process for subsequent dose exploration decision.

Part A Group 3 Arm A - Day 1 and 4 Venetoclax Combination Dose Escalation

In Group 3 Arm A, AZD2811 is planned to be administered at 200 mg IV on Day 1 and Day 4 every 28 days (Q4W) and venetoclax is planned to be given (with a meal and water) at a dose of 100 mg orally (PO) on Day 1 and ramping up to 200 mg (PO) on Days 2-28 for the 1st cycle. The third participant in cohort 1 (AZD2811 at 200 mg) will only be enrolled after the first 2 participants have received ≥2 weeks of treatment and have shown no evidence of toxicity observed to be compatible with a DLT.

Further dose escalations of AZD2811 in Group 3 Arm A will occur at the discretion of the SRC.

Part A Group 3 Arm B - Day 1, 4, 15, and 18 Venetoclax Combination Dose Escalation

If data from Groups 1 and/or 2 suggest that participants could benefit from a more intense AZD2811 dosing regimen, a schedule of venetoclax with AZD2811 dosing on Days 1, 4, 15 and 18 (see below) may be explored.

Group 3 Arm B will not exceed the registered venetoclax dose when combined with a starting dose of AZD2811 that is considered safe based on Group 3 Arm A observations. Subsequent cohorts will explore how to escalate AZD2811 in a more intensified schedule towards a recommended Phase 2 dose.

Part B - Dose Expansion

In Part B approximately 18 AML participants (6 additional participants in each group \[AZD2811 monotherapy, Group 1\], \[AZD2811 in the azacitidine combination setting, Group 2\], and \[AZD2811 and venetoclax combination, Group 3\]) will follow the affiliated dose/schedule from Part A that was found to be the most tolerable and/or efficacious.

Safety, Tolerability, Pharmacokinetics, and Efficacy of AZD2811 Nanoparticles as Monotherapy or in Combination in Acute Myeloid Leukemia Participants.

A Phase I/II, Open-Label, Multicentre 2-Part Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of AZD2811 as Monotherapy or in Combination in Treatment-Naïve or Relapsed/Refractory Acute Myeloid Leukaemia Patients Not Eligible for Intensive Induction 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.

A DLT was defined as any adverse event (AE) not related to the underlying leukaemia requiring treatment interruption for \> 21 days, any Grade 5 AE, Grade 4 neutropenia or thrombocytopenia lasting \>= 42 days from start of cycle in absence of evidence of active leukaemia, any \>= Grade 3 non-haematological AE (except Grade 3 nausea, vomiting, mucositis, stomatitis or diarrhoea that was controlled within 4 days and Grade 3 elevations in alanine aminotransferase/ aspartate aminotransferase that return to meet initial eligibility criteria within 7 days of study drug interruption), or any other clinically significant and/or unacceptable AE that does not respond to supportive care, results in a disruption of dosing schedule for \> 7 days, or was judged as a DLT by Investigator in collaboration with the Medical Monitor. An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. There will be no updated results for this outcome measures at the time of end of study.

Participants with abnormal clinical laboratory parameters reported as Grade 4 TEAEs are reported. Laboratory analysis included hematology, clinical chemistry, and urinalysis.

hematology, coagulation, chemistry, and urinalysis parameters over time are reported.

Total complete remission included CR and CR with incomplete recovery (CRi). The CR is defined as bone marrow blasts \<5%, absence of blasts with Auer rods, absence of extramedullary disease, absolute neutrophil count \>1.0 × 10/L, platelet count \>100 × 10/L, and independence of red cell transfusions. The CRi includes all CR criteria except for residual neutropenia (\<1.0 × 10/L) or thrombocytopenia (\<100 × 10/L).

The ORR included CR, CRi, and partial remission (PR). The CR is defined as bone marrow blasts \<5%, absence of blasts with Auer rods, absence of extramedullary disease, absolute neutrophil count \>1.0 × 10/L, platelet count \>100 × 10/L, and independence of red cell transfusions. The CRi includes all CR criteria except for residual neutropenia (\<1.0 × 10/L) or thrombocytopenia (\<100 × 10/L). The PR is defined as all hematologic criteria of CR (absolute neutrophil count \>1.0 × 10/L, platelet count \>100 × 10/L, and independence of red cell transfusions), decrease of bone marrow blast percentage to 5% to 25%, and decrease of pre-treatment bone marrow blast percentage by at least 50%.

The PR is defined as all hematologic criteria of CR (absolute neutrophil count \>1.0 × 10/L, platelet count \>100 × 10/L, and independence of red cell transfusions), decrease of bone marrow blast percentage to 5% to 25%, and decrease of pre-treatment bone marrow blast percentage by at least 50%.

Participants with \>50% change in myleloblasts from baseline are reported.

Carcinoma, Small Cell

Etoposide

Carboplatin

Cisplatin

Durvalumab

Etoposide phosphate

Antineoplastic Agents, Immunological

Induction:

Durvalumab + Platinum Chemotherapy (Carboplatin or cisplatin \& Etoposide)

Maintenance:

AZD2811 + Durvalumab

IV infusions through induction phase.

IV infusions through maintenance phase until PD or other discontinuation criteria.

IV infusions through maintenance phase until PD or other discontinuation criteria.

IV infusions through induction phase if chosen by Investigator.

A Phase II Multicenter, Open-Label, Single Arm Study to Determine the Efficacy, Safety and Tolerability of AZD2811 and Durvalumab Combination as Maintenance Therapy After Induction with Platinum-Based Chemotherapy Combined with Durvalumab, for the First-Line Treatment of Patients with Extensive Stage Small-Cell Lung Cancer.

Primary objective of this study is to evaluate the efficacy of AZD2811 and durvalumab in patients who have not progressed following induction therapy with platinum-based chemotherapy combined with durvalumab.

This is an open-label, single arm study. Patients will be treated in an induction phase with platinum-based induction therapy and durvalumab. At the end of this induction period, participants will be assessed for disease progression, per RECIST v1.1.

Participants who have not progressed per RECIST v1.1 at the end of the induction phase will roll over into the maintenance phase of the trial, where patients will commence AZD2811 and durvalumab combination.

Participants will be treated with AZD2811 and durvalumab as maintenance therapy until confirmed progressive disease, start of non-protocol defined anticancer therapy, unacceptable toxicity, or withdrawal of consent.

If study intervention is permanently discontinued, the participant will remain in the study to be evaluated for safety assessment, as well as for confirmed disease progression and for survival.

Targeted population are adult patients (aged ≥18 years) with histologically or cytologically documented extensive disease (American Joint Committee on Cancer Stage (7th edition) IV SCLC \[T any, N any,M1 a/b\]), or T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan. Patients must have WHO/ECOG performance status of 0 or 1.

Tumor assessments will be performed at Screening as baseline with follow-up every 6 weeks ± 1 week for the first 36 weeks, and then every 8 weeks ±1 week until confirmed objective disease progression.

Study of AZD2811 + Durvalumab in ES-SCLC

A Phase II Multicenter, Open-Label, Single Arm Study to Determine the Efficacy, Safety and Tolerability of AZD2811 and Durvalumab Combination as Maintenance Therapy After Induction With Platinum-Based Chemotherapy Combined With Durvalumab, for the First-Line Treatment of Patients With Extensive Stage Small-Cell Lung Cancer

Incidence of adverse events as measured by CTCAE 5.0

The EORTC QLQ-C30 consists of 30 questions that can be combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 6 individual items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties), and a global measure of health status. The EORTC QLQ-C30 will be scored according to the EORTC QLQ-C30 Scoring Manual.

Quality of life issues are assessed using a four-point scale (1= not at all, 2 = a little, 3 = quite a bit, 4 = very much), apart from two questions which are measured between 1 (Very Poor) to 7 (Excellent).

The EORTC QLQ-LC13 is a 13-item questionnaire comprised of 1 symptom scale assessing dysponea, and a series of single questions assessing cough, haemoptysis, sore mouth, dysphagis, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, and use of pain medication. All items are assessed using a Likert four-point scale (1= not at all to 4 = very much).

Scoring will be done according to the EORTC QLQ-C30 Scoring Manual (Fayers et al., 2001). A high score for a symptom scale or single item represents a high level of symptomology or problems.

Part A dose-escalation will evaluate the safety and tolerability of AZD2811 monotherapy at increasing doses in patients with advanced solid tumours. Patients will receive AZD2811 on Days 1 and 4 of a 28-day cycle or Day 1 only in cycles of either 21 or 28 days.

Part B will include patients with relapsed or refractory small-cell lung cancer (SCLC). Patients will receive AZD2811 monotherapy at the recommended Phase 2 dose (RP2D).

The study will be conducted in 2 parts, dose-escalation (A) and dose-expansion (B). All patients in both parts of the study with receive AZD2811.

Howard A. Burris, III, M.D.

This Phase I study is primarily designed to evaluate the safety and tolerability of AZD2811 at increasing doses in patients with advanced solid tumours and for whom no standard of care exists. The study will be conducted in two parts, a dose-escalation phase (Part A) and a dose expansion phase (Part B). During Part A, the dose-escalation phase, patient enrolment will proceed according to a 3+3 design where the maximum tolerated dose (MTD) or the recommended Phase II dose (RP2D) could be identified. The study will also characterize the pharmacokinetic (PK) profile of AZD2811 and will explore the potential biological activity by assessing anti-tumour activity in patients. Part B will further explore PK parameters, safety, tolerability, and preliminary anti-tumour activity of the AZD2811 RP2D as monotherapy (Group 1) in patients with relapsed/refractory SCLC.

This is a first-time-in-patient (FTIP) study with the nanoparticle formulation of AZD2811 primarily designed to evaluate the safety and tolerability of AZD2811 at increasing doses in patients with advanced solid tumours and for whom no standard of care exists.

The study will be conducted in two parts: Part A dose-escalation and Part B dose-expansion. In Part A, the dose-escalation phase, patient enrolment has proceeded according to a 3+3 design in order to identify the maximum-tolerated dose (MTD) or recommended Phase 2 dose (RP2D). AZD2811 monotherapy has been administered IV to patients with advanced solid tumours on Days 1 and 4 of a 28-day cycle in 6 dose levels without any relevant toxicities in the first 5 patient cohorts. In Cohort 6 (200 mg), grade 4 asymptomatic neutropenia was observed, and a dose-limiting toxicity was observed in 1 patient of the 5 evaluable patients. In Cohort 7 AZD2811 (200 mg) was given on Day 1 only of a 28-day cycle; in Cohort 8 AZD2811 (200 mg) was given on Day 1 only of a 21-day cycle. In Cohort 9, the AZD2811 dose was escalated to 400 mg on Day 1 every 21 days.

The Safety Review Committee (SRC) will review the safety and tolerability of AZD2811 for each cohort and schedule to determine the next cohorts. The study will also characterize the pharmacokinetic (PK) profile of AZD2811 and will explore potential biological activity by assessing anti-tumour activity in patients.

Once the MTD is established, Part B the dose expansion phase will continue to explore PK parameters, safety, tolerability, and preliminary anti-tumour activity of the AZD2811 RP2D as monotherapy in 21 patients with relapsed/refractory SCLC.

A Phase I Study of Safety, Tolerability, and PK of AZD2811 in Patients With Advanced Solid Tumors.

A Phase I, Open-Label, Multicentre Dose Escalation Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD2811 in Patients With Advanced Solid Tumours.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Maximum Tolerated Dose (MTD) will be determined in Part A of the study by assessing the incidence of Dose Limiting Toxicities (DLTs), adverse events, and abnormal laboratory results.

DLT is defined as:

1. Grade 4 neutropenia for \> 7 days, or febrile neutropenia.
2. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia with bleeding.
3. Concurrent Grade ≥3 total bilirubin, ALT or AST or alkaline phosphatase lasting \> 48 hours, or any change in liver function test results consistent with Hy's Law.
4. Grade ≥3 non-hematologic AE except: a) Grade 3 diarrhoea controlled within 4 days with standard supportive care, b) Grade 3 elevations in ALT/AST that return to meet initial eligibility criteria within 7 days of study drug interruption.
5. Inability to receive all doses in Cycle 1 due to treatment-related toxicity.
6. Non-haematologic toxicity of ≥ Grade 2 (at any time during treatment) that, in the judgment of the Investigator and the Medical Monitor, is dose limiting.

Maximum Tolerated Dose (MTD) will be determined in Part A of the study by assessing the incidence of Dose Limiting Toxicities (DLTs), adverse events, and abnormal laboratory results.

At least 3 evaluable patients will be enrolled at each dose level (3+3 design) and will be evaluated for 21 or 28 days before escalation to the next dose level can occur. If one patient experiences a DLT, an additional 3 patients will be treated with the same dose. Therefore, a maximum of up to 6 patients may be enrolled per dose level.

PK parameters will be derived by non-compartment analysis.

Baseline tumour imaging studies \[computerized tomography (CT)\] scan of the chest and abdomen/pelvis) will be performed within 28 days prior to the first dose of study drug (AZD2811) and will be repeated at the completion of Cycle 2 (Week 6 or Week 8) according the RECIST v1.1.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
AZD 2811 Monotherapy in Relapsed Small Cell Lung Cancer Patients [SUKSES-N3]	NCT03366675	Small Cell Lung...	AZD2811	20 Years -	Samsung Medical Center
Safety, Tolerability, Pharmacokinetics, and Efficacy of AZD2811 Nanoparticles as Monotherapy or in Combination in Acute Myeloid Leukemia Participants.	NCT03217838	Acute Myeloid L...	AZD2811 Azacitidine Venetoclax	18 Years - 130 Years	AstraZeneca
AZD 2811 Monotherapy in Relapsed Small Cell Lung Cancer Patients [SUKSES-N3]	NCT03366675	Small Cell Lung...	AZD2811	20 Years -	Samsung Medical Center
Study of AZD2811 + Durvalumab in ES-SCLC	NCT04745689	Small-Cell Lung...	Durvalumab AZD2811 Carboplatin Cisplatin Etoposide	18 Years - 130 Years	AstraZeneca
Safety, Tolerability, Pharmacokinetics, and Efficacy of AZD2811 Nanoparticles as Monotherapy or in Combination in Acute Myeloid Leukemia Participants.	NCT03217838	Acute Myeloid L...	AZD2811 Azacitidine Venetoclax	18 Years - 130 Years	AstraZeneca
Study of AZD2811 + Durvalumab in ES-SCLC	NCT04745689	Small-Cell Lung...	Durvalumab AZD2811 Carboplatin Cisplatin Etoposide	18 Years - 130 Years	AstraZeneca
Safety, Tolerability, Pharmacokinetics, and Efficacy of AZD2811 Nanoparticles as Monotherapy or in Combination in Acute Myeloid Leukemia Participants.	NCT03217838	Acute Myeloid L...	AZD2811 Azacitidine Venetoclax	18 Years - 130 Years	AstraZeneca
A Phase I Study of Safety, Tolerability, and PK of AZD2811 in Patients With Advanced Solid Tumors.	NCT02579226	Advanced Solid ...	AZD2811	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for azd2811

Every month we try and update this database with for azd2811 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 azd2811

Every month we try and update this database with for azd2811 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 azd2811 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.