Lymphoma, Peripheral T-Cell Lymphoma, Solid Tumor
Conditions
Brief summary
This study evaluates the anti-tumor effects of ALRN-6924 in patients with advanced solid tumors or lymphomas with WT TP53.
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.
Interventions
DRUGALRN-6924
ALRN-6924 will be administered as an IV infusion
Sponsors
Aileron Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 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, Expansion | From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days | Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0 |
| Determine the Maximum Tolerated Dose (MTD) of ALRN-6924 in Adult Patients With Advanced Solid Tumors or Lymphomas | From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days | Determine the maximum tolerated dose (MTD) |
| Determine Overall Response Rate | From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days | 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
| Measure | Time frame | Description |
|---|---|---|
| Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days | 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). |
| Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 8 weeks | Time of Peak Plasma Concentration (Tmax) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Regimen A (DR-A) Escalation (0.16 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle.
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 5 |
| Dose Regimen A (DR-A) Escalation (0.32 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle.
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 3 |
| Dose Regimen A (DR-A) Escalation (0.64 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle.
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 4 |
| Dose Regimen A (DR-A) Escalation (1.25 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle.
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 3 |
| Dose Regimen A (DR-A) Escalation (2.10 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle.
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 6 |
| Dose Regimen A (DR-A) Escalation (3.10 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle.
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 9 |
| Dose Regimen A (DR-A) Escalation (4.40 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle.
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 11 |
| Dose Regimen B (DR-B) Escalation (0.32 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 3 |
| Dose Regimen B (DR-B) Escalation (0.53 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 5 |
| Dose Regimen B (DR-B) Escalation (0.80 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 3 |
| Dose Regimen B (DR-B) Escalation (1.10 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 4 |
| Dose Regimen B (DR-B) Escalation (1.50 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 4 |
| Dose Regimen B (DR-B) Escalation (2.00 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 5 |
| Dose Regimen B (DR-B) Escalation (2.70 mg/kg) Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 4, 8 and 11 of a 21-day cycle
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 6 |
| Dose Regimen A (DR-A) PTCL Expansion Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 8 and 15 of a 28-day cycle.
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 21 |
| Dose Regimen C (DR-C) PTCL Expansion Drug: ALRN-6924 Weight-based-dosing administered IV on days 1, 3 and 5 of a 21-day cycle
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 16 |
| Combination With Palbociclib Expansion 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
ALRN-6924: ALRN-6924 will be administered as an IV infusion | 34 |
| Total | 142 |
Baseline characteristics
| Characteristic | Dose Regimen A (DR-A) Escalation (0.16 mg/kg) | Total | Combination With Palbociclib Expansion | Dose Regimen C (DR-C) PTCL Expansion | Dose Regimen A (DR-A) PTCL Expansion | Dose Regimen B (DR-B) Escalation (2.70 mg/kg) | Dose Regimen B (DR-B) Escalation (2.00 mg/kg) | Dose Regimen B (DR-B) Escalation (1.50 mg/kg) | Dose Regimen B (DR-B) Escalation (1.10 mg/kg) | Dose Regimen B (DR-B) Escalation (0.80 mg/kg) | Dose Regimen B (DR-B) Escalation (0.53 mg/kg) | Dose Regimen B (DR-B) Escalation (0.32 mg/kg) | Dose Regimen A (DR-A) Escalation (4.40 mg/kg) | Dose Regimen A (DR-A) Escalation (3.10 mg/kg) | Dose Regimen A (DR-A) Escalation (2.10 mg/kg) | Dose Regimen A (DR-A) Escalation (1.25 mg/kg) | Dose Regimen A (DR-A) Escalation (0.64 mg/kg) | Dose Regimen A (DR-A) Escalation (0.32 mg/kg) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 15.04 | 58.5 years STANDARD_DEVIATION 13.4 | 58.7 years STANDARD_DEVIATION 11.77 | 59.5 years STANDARD_DEVIATION 14.21 | 59.8 years STANDARD_DEVIATION 16.62 | 49.3 years STANDARD_DEVIATION 14.97 | 56.0 years STANDARD_DEVIATION 17.78 | 55.3 years STANDARD_DEVIATION 1.53 | 65.2 years STANDARD_DEVIATION 8.64 | 54.7 years STANDARD_DEVIATION 4.04 | 58.4 years STANDARD_DEVIATION 12.76 | 58.9 years STANDARD_DEVIATION 12.75 | 61.5 years STANDARD_DEVIATION 11.01 | 59.3 years STANDARD_DEVIATION 13.17 | 53.8 years STANDARD_DEVIATION 13.75 | 66.3 years STANDARD_DEVIATION 9.02 | 64.0 years STANDARD_DEVIATION 5.29 | 50.7 years STANDARD_DEVIATION 22.37 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 12 Participants | 4 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 120 Participants | 30 Participants | 12 Participants | 18 Participants | 5 Participants | 5 Participants | 4 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 11 Participants | 7 Participants | 5 Participants | 2 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 10 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 6 Participants | 1 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 27 Participants | 3 Participants | 5 Participants | 6 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 7 Participants | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 101 Participants | 28 Participants | 8 Participants | 12 Participants | 5 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants | 4 Participants | 2 Participants | 8 Participants | 7 Participants | 4 Participants | 2 Participants | 2 Participants | 1 Participants |
| Region of Enrollment United States | 5 participants | 142 participants | 34 participants | 16 participants | 21 participants | 6 participants | 5 participants | 4 participants | 4 participants | 3 participants | 5 participants | 3 participants | 11 participants | 9 participants | 6 participants | 3 participants | 4 participants | 3 participants |
| Sex: Female, Male Female | 2 Participants | 75 Participants | 19 Participants | 8 Participants | 12 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 3 Participants | 6 Participants | 4 Participants | 4 Participants | 1 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 67 Participants | 15 Participants | 8 Participants | 9 Participants | 4 Participants | 3 Participants | 2 Participants | 2 Participants | 1 Participants | 3 Participants | 0 Participants | 5 Participants | 5 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 3 | 0 / 4 | 0 / 3 | 0 / 6 | 0 / 9 | 0 / 11 | 0 / 3 | 0 / 5 | 0 / 3 | 0 / 4 | 0 / 4 | 0 / 5 | 0 / 6 | 0 / 21 | 0 / 16 | 5 / 34 |
| other Total, other adverse events | 5 / 5 | 3 / 3 | 4 / 4 | 3 / 3 | 6 / 6 | 9 / 9 | 11 / 11 | 3 / 3 | 5 / 5 | 3 / 3 | 4 / 4 | 4 / 4 | 5 / 5 | 6 / 6 | 19 / 21 | 15 / 16 | 34 / 34 |
| serious Total, serious adverse events | 0 / 5 | 0 / 3 | 0 / 4 | 1 / 3 | 0 / 6 | 2 / 9 | 4 / 11 | 0 / 3 | 1 / 5 | 0 / 3 | 0 / 4 | 0 / 4 | 0 / 5 | 0 / 6 | 7 / 21 | 7 / 16 | 5 / 34 |
Outcome results
Primary
Determine Overall Response Rate
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).
Time frame: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Regimen A (DR-A) Escalation (0.16 mg/kg) | Determine Overall Response Rate | 2 Participants |
| Dose Regimen A (DR-A) Escalation (0.32 mg/kg) | Determine Overall Response Rate | 2 Participants |
Primary
Determine the Maximum Tolerated Dose (MTD) of ALRN-6924 in Adult Patients With Advanced Solid Tumors or Lymphomas
Determine the maximum tolerated dose (MTD)
Time frame: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Regimen A (DR-A) Escalation (0.16 mg/kg) | Determine the Maximum Tolerated Dose (MTD) of ALRN-6924 in Adult Patients With Advanced Solid Tumors or Lymphomas | 3.1 mg/kg |
| Dose Regimen A (DR-A) Escalation (0.32 mg/kg) | Determine the Maximum Tolerated Dose (MTD) of ALRN-6924 in Adult Patients With Advanced Solid Tumors or Lymphomas | NA mg/kg |
Primary
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
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
Time frame: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Regimen A (DR-A) Escalation (0.16 mg/kg) | 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 | 5 Participants |
| Dose Regimen A (DR-A) Escalation (0.32 mg/kg) | 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 | 3 Participants |
| Dose Regimen A (DR-A) Escalation (0.64 mg/kg) | 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 | 4 Participants |
| Dose Regimen A (DR-A) Escalation (1.25 mg/kg) Escalation | 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 | 3 Participants |
| Dose Regimen A (DR-A) Escalation (2.10 mg/kg) Escalation | 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 | 6 Participants |
| Dose Regimen A (DR-A) Escalation (3.10 mg/kg) Escalation | 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 | 9 Participants |
| Dose Regimen A (DR-A) Escalation (4.40 mg/kg) Escalation | 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 | 11 Participants |
| Dose Regimen B (DR-B) Escalation (0.32 mg/kg) | 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 | 3 Participants |
| Dose Regimen B (DR-B) Escalation (0.53 mg/kg) | 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 | 5 Participants |
| Dose Regimen B (DR-B) Escalation (0.80 mg/kg) | 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 | 3 Participants |
| Dose Regimen B (DR-B) Escalation (1.10 mg/kg) | 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 | 4 Participants |
| Dose Regimen B (DR-B) Escalation (1.50 mg/kg) | 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 | 4 Participants |
| Dose Regimen B (DR-B) Escalation (2.00 mg/kg) | 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 | 5 Participants |
| Dose Regimen B (DR-B) Escalation (2.70 mg/kg) | 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 | 6 Participants |
| Dose Regimen A (DR-A) PTCL Expansion | 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 | 21 Participants |
| Dose Regimen C (DR-C) PTCL Expansion | 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 | 16 Participants |
| Combination With Palbociclib Expansion (DR-A) | 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 | 34 Participants |
Primary
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, Expansion
Number of participants with treatment-related adverse events as assessed by CTCAE v.4.0
Time frame: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Regimen A (DR-A) Escalation (0.16 mg/kg) | 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, Expansion | 21 Participants |
| Dose Regimen A (DR-A) Escalation (0.32 mg/kg) | 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, Expansion | 16 Participants |
| Dose Regimen A (DR-A) Escalation (0.64 mg/kg) | 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, Expansion | 34 Participants |
Secondary
Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response
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).
Time frame: From Day 1 of treatment until 30 days after the last cycle of treatment (each cycle in DR-A is 28 days, DR-B and DR-C is 21 days), an average of 138 Days
Population: The efficacy evaluable population was defined as those patients who met all of the following criteria: (1) Received at least 1 dose of ALRN-6924 at a dose level at least 0.8 mg/kg per infusion (2) Had at least 1 postbaseline evaluation or had clinical disease progression (3) Were TP53 wild type or indeterminate (as assessed by the central laboratory; if not assessed by central laboratory, as assessed by the local laboratory.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Regimen A (DR-A) Escalation (0.16 mg/kg) | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 0 Participants |
| Dose Regimen A (DR-A) Escalation (0.32 mg/kg) | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 0 Participants |
| Dose Regimen A (DR-A) Escalation (0.64 mg/kg) | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 0 Participants |
| Dose Regimen A (DR-A) Escalation (1.25 mg/kg) Escalation | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 0 Participants |
| Dose Regimen A (DR-A) Escalation (2.10 mg/kg) Escalation | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 1 Participants |
| Dose Regimen A (DR-A) Escalation (3.10 mg/kg) Escalation | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 0 Participants |
| Dose Regimen A (DR-A) Escalation (4.40 mg/kg) Escalation | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 1 Participants |
| Dose Regimen B (DR-B) Escalation (0.32 mg/kg) | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 0 Participants |
| Dose Regimen B (DR-B) Escalation (0.53 mg/kg) | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 0 Participants |
| Dose Regimen B (DR-B) Escalation (0.80 mg/kg) | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 1 Participants |
| Dose Regimen B (DR-B) Escalation (1.10 mg/kg) | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 0 Participants |
| Dose Regimen B (DR-B) Escalation (1.50 mg/kg) | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 0 Participants |
| Dose Regimen B (DR-B) Escalation (2.00 mg/kg) | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 0 Participants |
| Dose Regimen B (DR-B) Escalation (2.70 mg/kg) | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 1 Participants |
| Dose Regimen A (DR-A) PTCL Expansion | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 1 Participants |
| Dose Regimen C (DR-C) PTCL Expansion | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 1 Participants |
| Combination With Palbociclib Expansion (DR-A) | Assess Additional Measures of Anti-tumor Activity, Including Duration of Response, Progression Free Survival, Overall Survival and Time to Response | 0 Participants |
Secondary
Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas
Time of Peak Plasma Concentration (Tmax)
Time frame: 8 weeks
Population: The Pharmacokinetic Analysis Population included all subjects who received at least one dose of ALRN-6924 with sufficient plasma sample data to assess PK parameters, and with no major protocol violations. Plasma samples for subjects in the Combination With Palbociclib Expansion arm were collected but will not be processed or analyzed due to a protocol-level decision for this expansion arm to discontinue pharmacokinetic data collection.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Regimen A (DR-A) Escalation (0.16 mg/kg) | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.03 hour |
| Dose Regimen A (DR-A) Escalation (0.32 mg/kg) | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.13 hour |
| Dose Regimen A (DR-A) Escalation (0.64 mg/kg) | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.04 hour |
| Dose Regimen A (DR-A) Escalation (1.25 mg/kg) Escalation | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.04 hour |
| Dose Regimen A (DR-A) Escalation (2.10 mg/kg) Escalation | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.29 hour |
| Dose Regimen A (DR-A) Escalation (3.10 mg/kg) Escalation | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.12 hour |
| Dose Regimen A (DR-A) Escalation (4.40 mg/kg) Escalation | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.06 hour |
| Dose Regimen B (DR-B) Escalation (0.32 mg/kg) | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.17 hour |
| Dose Regimen B (DR-B) Escalation (0.53 mg/kg) | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.22 hour |
| Dose Regimen B (DR-B) Escalation (0.80 mg/kg) | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.08 hour |
| Dose Regimen B (DR-B) Escalation (1.10 mg/kg) | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.29 hour |
| Dose Regimen B (DR-B) Escalation (1.50 mg/kg) | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.08 hour |
| Dose Regimen B (DR-B) Escalation (2.00 mg/kg) | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.30 hour |
| Dose Regimen B (DR-B) Escalation (2.70 mg/kg) | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.03 hour |
| Dose Regimen A (DR-A) PTCL Expansion | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.05 hour |
| Dose Regimen C (DR-C) PTCL Expansion | Determine Pharmacokinetic Parameters of ALRN-6924 When Administered to Patients With Advanced Solid Tumors or Lymphomas | 0.05 hour |