First Patient Enrolled in Phase 1b Schedule Optimization of ALRN-6924

The first patient has been enrolled in the open-label phase 1b schedule optimization part of the ongoing phase 1b/2 clinical trial evaluating ALRN-6924’s potential to protect patients against chemotherapy-induced toxicities, according to Aileron Therapeutics, the developer of the agent.¹

Patients enrolled in this open-label trial have p53-mutated extensive disease small cell lung cancer (SCLC) and are being treated with second-line topotecan (Hycamtin) following administration of ALRN-6924.

“We were highly encouraged by the strong chemoprotective effect of ALRN-6924 seen in the dose optimization part of this study as previously reported, as it reinforces our belief that ALRN-6924 can selectively induce cell cycle arrest to protect cancer patients from the toxic side effects of chemotherapy,” Vojo Vukovic, MD, PhD, chief medical officer of Aileron, said in a press release. “The schedule optimization part of the trial is intended to inform whether ALRN-6924 given 6 hours before topotecan can further enhance the protective effects we have observed when giving our drug 24 hours before topotecan.”

The ongoing phase 1b/2 study is designed to determine the optimal dose and schedule of ALRN-6924 administration to reduce chemotherapy toxicities such as severe anemia, thrombocytopenia, and neutropenia caused by topotecan in patients with SCLC.

In the dose optimization portion of the study, which enrolled 18 patients, ALRN-6924 was administered at 3 dose levels (0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg) 24 hours before each dose of topotecan on days 1 through 5 of every 21-day treatment cycle. An expansion cohort of the dose optimization part of the trial at the 0.3 mg/kg dose level is ongoing.

In June 2020, Aileron announced positive interim findings from this part of the trial.² Key findings from the interim analysis of the phase 1b optimization portion of the trial included:

• Patients treated with 0.3 mg/kg of ALRN-6924 demonstrated the lowest rate of NCI CTC grade 3/4 hematological adverse events, including 17% with anemia, 33% with thrombocytopenia, and 67% with neutropenia, across all treatment cycles.
• None of the patients treated with 0.3 mg/kg of ALRN-6924 required transfusions of red blood cells or platelets.
• Across all 3 dose levels, patients showed NCI CTC grade 3/4 hematological adverse events, including 24% with anemia, 35% with thrombocytopenia, and 88% with neutropenia.
• Across all three dose levels, no patients experienced febrile neutropenia or NCI CTC grade 3/4 nausea, vomiting, diarrhea, or fatigue, which are the severe toxicities commonly associated with topotecan-treatment in this patient population.

In the schedule optimization part, ALRN-6924 is being administered at 2 dose levels of 0.3 and 0.6 mg/kg 6 hours before each dose of topotecan on days 1 through 5 of every 21-day treatment cycle. The company indicated that they anticipate enrolling approximately 20 patients in this portion of the study.

“Chemotherapy remains a critical cornerstone treatment for millions of cancer patients. Unfortunately, in the process of killing cancer cells, chemotherapy inadvertently harms healthy cells, too,” Manuel Aivado, MD, PhD, president and CEO of Aileron Therapeutics, explained in a press release. “This leads to a multitude of common, damaging, severe toxicities. We treat healthy cells ahead of chemotherapy to prevent those toxicities, importantly, without interrupting chemotherapy’s potent onslaught against cancer cells. ALRN-6924 could dramatically improve patients’ quality of life by improving their tolerance to chemotherapy.”

As previously reported, Aileron intends to report topline data from the schedule optimization and final data from the dose optimization parts of the trial in the fourth quarter of 2020. The company predicts that these results will allow the determination of a recommended ALRN-6924 dose and schedule for subsequent trials.

Reference:

1. Aileron Therapeutics Initiates Enrollment in Schedule Optimization Part of Phase 1b/2 Study of ALRN-6924 as a Chemoprotection Agent in Small Cell Lung Cancer (SCLC) Patients Being Treated with Topotecan [news release]. Watertown, Massachusetts. Published June 29, 2020. globenewswire.com/news-release/2020/06/29/2054704/0/en/Aileron-Therapeutics-Initiates-Enrollment-in-Schedule-Optimization-Part-of-Phase-1b-2-Study-of-ALRN-6924-as-a-Chemoprotection-Agent-in-Small-Cell-Lung-Cancer-SCLC-Patients-Being-Tr.html. Accessed June 29, 2020.

2. Aileron Therapeutics Announces Positive Interim Results from Phase 1b/2 Clinical Trial of ALRN-6924 for the Prevention of Topotecan-induced Toxicities During Treatment for Small Cell Lung Cancer [news release]. Watertown, Massachusetts. Published June 1, 2020. globenewswire.com/news-release/2020/06/01/2041365/0/en/Aileron-Therapeutics-Announces-Positive-Interim-Results-from-Phase-1b-2-Clinical-Trial-of-ALRN-6924-for-the-Prevention-of-Topotecan-induced-Toxicities-During-Treatment-for-Small-Ce.html. Accessed June 29, 2020.