Small Cell Lung Cancer and Non small cell lung cancer MedDRA version: 21.1 Level: PT Classification code 10041067 Term: Small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: ALRN-6924
Product Code: ALRN-6924
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: pending
Other descriptive name: ALRN-6924
Concentration unit: mg/ml milligram(s)/milli
Sponsors
Aileron Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: SCLC 1. Males and females age 18 years or older. 2. Ability to understand the requirements of this clinical trial and willingness to provide written informed consent 3. Histopathological confirmation of ED SCLC that has recurred or been refractory to one line of treatment with standard platinum-based chemotherapy or immuno-chemotherapy. Patients who received immunotherapy after platinum-based chemotherapy remain eligible. 4. Mutated TP53: no wild type (WT) TP 53 gene copies within the tumor (i.e., biallelic mutation, biallelic deletion, or mutation/deletion), as assessed by next generation sequencing (NGS) 5. Measurable disease using RECIST 1.1 6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 7. Adequate hematological status: a. absolute neutrophil count (ANC) =1500/?L b. platelet count =100,000/?L c. hemoglobin =9.0 g/dL 8. Adequate hepatic and renal function: a. total bilirubin =1.5 X upper limit of normal (ULN) or = 3 X ULN in the presence of Gilbert syndrome or liver metastases b. alkaline phosphatase (ALP), aspartate aminotransferase (AST [SGOT]), and alanine aminotransferase (ALT [SGPT]) = 2.5 X ULN in the absence of liver metastases c. ALP, AST (SGOT), and ALT (SGPT) =5 X ULN in the presence of liver metastases d. serum creatinine <1.5 X ULN or calculated creatinine clearance = 40 mL/min (C&G or EDTA) 9. Recovery from the acute toxic effects of all prior therapies to Grade =1 10. The shorter of 5 half-lives or 4 weeks must have elapsed since any prior systemic therapy, unless no drug-drug interactions with study treatment would be anticipated and the patient had unequivocal radiologic disease progression during the prior line of therapy. 11. Males and female patients of child-bearing potential must agree to use an acceptable method of birth control for the duration of study treatment and for 3 months (male patients with female partner of child-bearing potential) or 6 months (female patients of child-bearing potential) following the last dose of study treatment. NSCL 1. Males and females age 18 years or older. 2. Ability to understand the requirements of this clinical trial and willingness to provide written informed consent. 3. Histopathological confirmation of Stage IV NSCLC of adenocarcinoma histology. Cytological diagnosis of NSCLC is acceptable if sufficient tumor tissue is available for p53 mutation analysis. FDA approved liquid biopsies are also acceptable. 4. Presence of p53 mutation(s) in tumor tissue or circulating cell free DNA as assessed by next generation sequencing (NGS). 5. Patients who are deemed to be good candidates for chemotherapy with carboplatin and pemetrexed, OR standard immunochemotherapy that includes carboplatin and pemetrexed, with a planned delivery of at least 4 chemotherapy treatment cycles. Concurrent use of bevacizumab as per local treatment practice, is permitted. 6. No prior systemic therapy for any stage NSCLC, including chemotherapy, immunotherapy or targeted drugs (e.g., inhibitors of EGFR, ALK, ROS, RET, HER2, BRAF etc.). 7. Absence of tumor genomic aberrations of EGFR, ALK or other actionable genomic aberrations, as per local standard of care. 8. Measurable disease using RECIST 1.1 9. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 10. Adequate hematological status without supportive care measures during screening period: a. ANC =1500/mL b. platelet count =100,000/mL hemoglobin =9.0 g/dL 11. Adequate hepatic and renal function: a. total bilirubin =
Exclusion criteria
Exclusion criteria: SCLC 1.Known hypersensitivity to any component of study treatment. 2. Presence of active and symptomatic central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable, with no evidence of radiographic or neurologic progression during the screening period and no requirement for steroids for at least 15 days before enrolment. 3. Advanced NSCLC tumors with EGFR mutations or ALK re-arrangement or other actionable genetic aberrations for which an approved targeted treatment is available. Patients who received prior treatment with EGFR or ALK inhibitors or other systemic drugs or immunotherapy for NSCLC are not eligible for participation. 4. Patients who are candidates for anti-PD-1 monotherapy in 1stline advanced NSCLC (e.g., tumors with high PD-L1 expression). 5. Patients who received prior systemic treatment for earlier stage NSCLC disease other than surgery, immunotherapy and/or localized radiotherapy. Patients who received neoadjuvant or adjuvant chemotherapy, or radiochemotherapy are not eligible for participation. 6. Uncontrolled intercurrent illness including but not limited to: a. Clinically significant, active, uncontrolled infection including human immunodeficiency virus (HIV), or hepatitis B or C i. Patients with HIV must be on effective antiretroviral therapy for = 4 weeks prior to enrollment and have HIV viral load < 400 copies/mL, have had no acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the past 12 months, and have CD4+ count = 350 cells/µL. ii. Patients with chronic hepatitis B virus (HBV) must be on antiviral therapy and have HBV viral load below the limits of detection. iii. Patients with hepatitis C virus (HCV) must be on or have completed antiviral therapy and have an HCV viral load below the limits of detection. b. Uncontrolled hypertension c. Uncontrolled diabetes mellitus 7. Serum albumin <30 g/L 8. Clinically significant electrolyte abnormalities 9. Clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling temporary pacemaker 10. History of prior malignancy; patients with a known malignancy that does not affect overall well-being and ability to participate in the study can be considered in consultation with the Medical Monitor. see more exclusion criteria in the protocol NSCL Exclusion Criteria: 1. Known hypersensitivity to any component of study treatment. 2. Presence of active and symptomatic central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable, with no evidence of radiographic or neurologic progression during the screening period and no requirement for steroids for at least 15 days before enrolment. 3. Advanced NSCLC tumors with EGFR mutations or ALK re-arrangement or other actionable genetic aberrations for which an approved targeted treatment is available. Patients who received prior treatment with EGFR or ALK inhibitors or other systemic drugs or immunotherapy for NSCLC are not eligible for participation. 4. Patients who are candidates for anti-PD-1 monotherapy in 1st-line advanced NSCLC (e.g., tumors with high PD-L1 expression). 5. Patients who received prior systemic treatment for earlier stage NSCLC disease other than surgery, immunotherapy and/or localized r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: SCLC, phase 1b To evaluate the safety and tolerability and determine the recommended Phase 2 dose (RP2D) and schedule of ALRN-6924 when administered to patients with TP53-mutated ED SCLC receiving topotecan as 2nd line treatment SCLC, phase 2 To evaluate the myelopreservation effects of ALRN-6924 when administered at the RP2D and schedule to patients with TP53-mutated ED SCLC undergoing 2nd line treatment with topotecan NSCLC To evaluate the preliminary myelopreservation effects of ALRN-6924 when administered to patients with TP53-mutated advanced NSCLC of adenocarcinoma histology receiving 1st_line treatment with carboplatin plus pemetrexed with or without immunotherapy ;Secondary Objective: SCLC • To evaluate the preliminary myelopreservation effects of ALRN-6924 when administered to patients with TP53-mutated ED SCLC undergoing 2nd line treatment with topotecan • To evaluate the efficacy of topotecan when administered as 2nd-line treatment for patients with TP53-mutated ED SCLC who are receiving supportive treatment with ALRN-6924 • To evaluate the pharmacokinetic (PK) profile of ALRN 6924 when administered with topotecan NSCLC • To evaluate the safety and tolerability of ALRN-6924 when administered to patients with TP53-mutated advanced NSCLC of adenocarcinoma histology receiving 1st line treatment with carboplatin plus pemetrexed with or without immunotherapy. • To evaluate the efficacy of 1st_line treatment with carboplatin plus pemetrexed with or without immunotherapy in patients with TP53-mutated advanced NSCLC of adenocarcinoma histology who are receiving supportive treatment with ALRN-6924 • To assess concentrations of ALRN-6924 in blood during treatment.;Primary end point(s): SCLC, phase 1b Proportion of patients with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3/4 treatment emergent adverse events (TEAEs) SCLC, phase 2 Proportion of patients with Grade = 3 neutropenia in Cycle 1 NSCL P | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): SCLC, phase 1b • Proportion of patients with Grade = 3 neutropenia in Cycle 1 SCLC, phase 2 • Proportion of patients with Grade = 3 neutropenia in Cycle 2 and beyond • Time to first incidence of Grade = 3 neutropenia • Duration of Grade = 3 neutropenia • Proportion of patients with Grade = 3 thrombocytopenia • Proportion of patients with Grade = 3 anemia • Proportion of patients with febrile neutropenia • Proportion of planned treatment cycles delayed due to toxicity • Proportion of patients with NCI CTCAE Grade 3/4 TEAEs • ORR by RECIST 1.1 • PFS • OS • PK parameters (e.g., AUC, Cmax, tmax, t1/2) of ALRN-6924 NSCLC • Proportion of patients with NCI CTCAE Grade 3/4 TEAEs • ORR by RECIST 1.1 • PFS • Concentrations of ALRN-6924 in blood on Days 0, 1, and 2 during Cycle 1;Timepoint(s) of evaluation of this end point: SCLC, phase 1b: Cycle 1 SCLC, phase 2: Cycle 2 and beyond NSCLC Full analysis Set: all enrolled patients who received at least one dose of ALRN-6924 or placebo and initiated chemotherapy or immunotherapy treatment Per Protocol Population: All patients who meet eligibility criteria, have received the assigned study drug treatment and have completed at least 4 treatment cycles with chemotherapy or immunochemotherapy and ALRN-6924 or placebo. Patients who do not complete at least 4 treatment cycles due to treatment-related toxicities are evaluable and will be included in the analysis. Patients who do not complete at least 4 treatment cycles due to disease progression or any reason other than treatment-related toxicity will not be included in the analysis. | — |
Countries
Bosnia and Herzegovina, Croatia, Netherlands, Poland, Serbia, Spain, United States
Contacts
Public ContactChristopher Caldwell
Aileron Therapeutics, Inc.
Outcome results
None listed