ALRN-6924 in Patients With Advanced Solid Tumors or Lymphomas

Sponsor

Aileron Therapeutics, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02264613

Collaborator

(none)

149

Enrollment

Locations

Arms

Actual Duration (Months)

11.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluates the anti-tumor effects of ALRN-6924 in patients with advanced solid tumors or lymphomas with WT TP53.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor Lymphoma Peripheral T-Cell Lymphoma	Drug: ALRN-6924	Phase 1/Phase 2

Detailed Description

Open label, multi center, Phase 1 (dose escalation) and Phase 2a (dose expansion) study design to evaluate safety, tolerability, PK, PD and anti-tumor effects of ALRN-6924, alone or in combination with palbociclib, in patients with advanced solid tumors or lymphomas with wild-type (WT) TP53. ALRN-6924 is a stabilized cell-permeating peptide designed to disrupt the interaction between the p53 tumor suppressor protein and its predominant endogenous inhibitors, murine double minute 2 (MDM2) and murine double minute X (MDMX).

The Phase 1 portion of the study will enroll adults with histologically or cytologically confirmed malignancies that are metastatic or unresectable and for which standard treatment(s) are not available or are no longer effective. The Phase 2a portion of the study consists of separate cohorts that will enroll distinct groups of patients with specific solid tumors and/or lymphomas to further investigate the clinical safety profile and potential efficacy of ALRN-6924 alone or in a combination regimen.

Treatment will continue until unacceptable toxicity, patient or physician decision to discontinue therapy or disease progression that is either symptomatic, rapidly progressive, requires urgent intervention or is associated with a decline in performance status.

Patients with PTCL have been selected as a group to be further studied in Phase 2a.

Patients with MDM2-amplified or MDM2/CDK4-co-amplified solid tumors have been selected as another group to be further studied in Phase 2a.

Study Design

Study Type:

Interventional

Actual Enrollment :

149 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2a Open-Label Study to Determine the Safety and Tolerability of ALRN-6924 Alone or in Combination in Patients With Advanced Solid Tumors or Lymphomas Expressing Wild-Type p53 Protein

Actual Study Start Date :

Oct 1, 2014

Actual Primary Completion Date :

Mar 1, 2020

Actual Study Completion Date :

Apr 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Regimen A (DR-A) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle.	Drug: ALRN-6924 ALRN-6924 will be administered as an IV infusion
Experimental: Dose Regimen B (DR-B) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle	Drug: ALRN-6924 ALRN-6924 will be administered as an IV infusion
Experimental: Dose Regimen C (DR-C) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 3 and 5 of a 21-day cycle	Drug: ALRN-6924 ALRN-6924 will be administered as an IV infusion
Experimental: Combination with palbociclib Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle Drug: Palbociclib Fixed-dose capsule administered orally on days 1 through 21 of a 28-day cycle	Drug: ALRN-6924 ALRN-6924 will be administered as an IV infusion

Outcome Measures

Primary Outcome Measures

Evaluate the safety and tolerability of ALRN-6924 in adult patients with advanced solid tumors or lymphomas with wild-type (WT) TP53 who are refractory to or intolerant of standard therapy, or for whom no standard therapy exists - Phase 1 [From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)]
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
Evaluate the safety and tolerability of ALRN-6924 in adult patients with advanced solid tumors or lymphomas with wild-type (WT) TP53 who are refractory to or intolerant of standard therapy, or for whom no standard therapy exists - Phase 2 [From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle is 28 days)]
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
Determine the maximum tolerated dose (MTD) - Phase 1 [From the first dose until the end of the first cycle (each cycle is 28 days)]
Determine the dose limiting toxicities (DLT) and the maximum tolerated dose (MTD) or the optimal biological dose (OBD) of ALRN-6924 in adult patients with advanced solid tumors or lymphomas
Determine Overall Response Rate - Phase 2 [From the first dose until the first documented date of progression or date of death from any cause, whichever comes first, assessed up to 100 months]
The proportion of efficacy-evaluable patients who achieve complete response (CR) or partial response (PR), per investigator assessment, in accordance with RECIST 1.1 or iRECIST (for solid tumor patients) or Response Assessment in Neuro-Oncology (RANO) criteria (for glioblastoma patients).

Secondary Outcome Measures

Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas [8 weeks]
Peak Plasma Concentration (Cmax)
Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas [8 weeks]
Area under the plasma concentration versus time curve (AUC)
Determine Pharmacokinetic parameters of ALRN-6924 when administered to patients with advanced solid tumors or lymphomas [8 weeks]
Time of Peak Plasma Concentration (Tmax)
Assess additional measures of anti-tumor activity, including duration of response, progression free survival, overall survival and time to response [From the first dose until the first documented date of progression or date of death from any cause, whichever comes first, assessed up to 100 months]
The proportion of efficacy-evaluable patients who achieve complete response (CR) or partial response (PR), per investigator assessment, in accordance with RECIST 1.1 or iRECIST (for solid tumor patients) or Response Assessment in Neuro-Oncology (RANO) criteria (for glioblastoma patients).
Assess additional pharmacologic properties, including biomarkers and immunogenicity [Up to 24 weeks]
The correlation of response with MDM2, MDMX, and/or CDK4 gene copy number and other genetic and protein biomarkers

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Histologically or cytologically confirmed solid tumor or lymphoma that is not amenable to standard therapies.
Cohort specific biomarkers, including confirmed or anticipated WT TP53 (Phase 1 and PTCL expansion cohorts) and MDM2-amplification or MDM2/CDK4-co-amplification (solid tumor expansion cohort)
At least one target lesion that is measurable by RECIST 1.1, RANO or IWG 2014, as appropriate for tumor type
ECOG (Eastern Cooperative Oncology Group) performance status 0-1
Adequate coagulation and hematologic function
Adequate hepatic and renal function
Sufficient wash out from prior therapies and recovery from all significant acute toxicities

Key Exclusion Criteria

Prior treatment with an MDM2 inhibitor, with protocol specified exceptions
Known hypersensitivity to any study drug component
Protocol specified cardiovascular risk factors
Clinically significant gastrointestinal bleeding within 6 months
Clinically significant third-space fluid accumulation
Active uncontrolled infection, including HIV/AIDS or Hepatitis B or C
HPV positive tumors
Second malignancy within two years, with protocol specified exceptions
Pregnancy or lactation

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Birmingham	Alabama	United States	35294
2	Duarte	California	United States	91010
3	Denver	Colorado	United States	80218
4	Sarasota	Florida	United States	34232
5	Tampa	Florida	United States	33612
6	Boston	Massachusetts	United States	02114
7	Boston	Massachusetts	United States	02215
8	Bronx	New York	United States	10461
9	New York	New York	United States	10065
10	Greenville	South Carolina	United States	29605
11	Nashville	Tennessee	United States	37203
12	Houston	Texas	United States	77030
13	Seattle	Washington	United States	98105

Sponsors and Collaborators

Aileron Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Aileron Therapeutics, Inc.

ClinicalTrials.gov Identifier:

NCT02264613

Other Study ID Numbers:

ALRN-6924-1-01

First Posted:

Oct 15, 2014

Last Update Posted:

Jul 14, 2020

Last Verified:

Jul 1, 2020

Additional relevant MeSH terms:

Lymphoma

Lymphoma, T-Cell, Peripheral

Study Results

No Results Posted as of Jul 14, 2020