A Phase 1b/2 Study of the Dual MDMX/MDM2 Inhibitor, ALRN-6924, for the Prevention of chemotherapy-induced Myelosuppressio

Completed

• Conditions: Myelopreservation during myelosuppressive chemotherapy with Topotecan; 10002086; 10029107

• Registration Number: NL-OMON49367
• Lead Sponsor: Aileron Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 4

Inclusion Criteria

Inclusion Criteria:
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.

Exclusion Criteria

Exclusion Criteria:
1. Known hypersensitivity to any component of study treatment including
mannitol, which is an excipient in topotecan.
2. More than one line of prior chemotherapy for ED SCLC (prior immunotherapy is
permitted, concurrent with or subsequent to firstline chemotherapy).
Previous treatment with platinum-based chemotherapy concomitant with
radiotherapy for limited disease is allowed if completed at least 6 months
prior to enrolment into the current trial.
3. Presence of active 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.
4. 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/*L.
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
5. Clinically significant electrolyte abnormalities
6. Clinically unstable cardiac disease, including unstable atrial fibrillation,
symptomatic bradycardia, unstable congestive heart failure, active myocardial
ischemia, or indwelling temporary pacemaker
7. 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.
8. Pregnant or lactating women
9. Hereditary angioedema of any severity or severe or life-threatening
angioedema due to any cause.
10. Major surgery (e.G. opening up a mesenchymal barrier) within 28 days of
enrolment. Please consult Medical monitor as needed
11. Significant weight loss (*15% body weight) within the 4 weeks prior to
enrolment.
12. Treatment with an investigational agent for any indication within the
shorter of 14 days or 5 half-lives, if the half-life is known
13. The required use of any concomitant medications that are predominantly
cleared by hepatobiliary transporters, organic anion transporter polypeptide
[OATP] members OATP1B1 and OATP1B3 on the day of the first ALRN-6924 infusion
to within 48 hours after the last ALRN-6924 infusion in a treatment cycle (see
Appendix A)
14. Other medications, severe acute/chronic medical or psychiatric condition,
or laboratory abnormality that may increase the risk associated with study
participation or study drug administration, or may interfere with the
interpretation of study results, and in the judgment of the investigator would
make the patient inappropriate for entry into this study

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Phase 1b<br /><br>Primary endpoint:<br /><br>- Proportion of patients with National Cancer Institute (NCI) Common<br /><br>Terminology Criteria for Adverse Events (CTCAE) Grade 3/4 treatment<br /><br>emergent adverse events (TEAEs)<br /><br><br /><br>Phase 2<br /><br>Primary endpoint:<br /><br>- Proportion of patients with Grade * 3 neutropenia in Cycle 1</p><br>