QUE Drug Candidate

Q-122 for the treatment of hot flashes in breast cancer patients.

Background 

QUE Oncology’s lead asset is Q-122. It is currently being developed for the treatment of hot flashes in women diagnosed with breast cancer who are receiving hormonal therapy. Q-122 is an orally available small molecule that has been investigated in several in vitro and in vivo pharmacology studies. The clinical results have shown that Q-122 has an excellent safety profile and warrants the need for further clinical studies to assess the efficacy of the drug in the treatment of hot flashes. 

 

Disease indication

Approximately 70% of breast cancer patients are estrogen receptor positive (ER+) or progesterone receptor positive (PR+) indicating that the growth and behaviour of the tumour is influenced by estrogen and/or progesterone. Treatment modalities used to manage hormone sensitive breast cancer may result in the long-term suppression of estrogen to control disease.  Suppression of estrogen in these patients results in a state of induced menopause. Significant menopausal symptoms, including debilitating hot flashes often occurs. The use of hormone replacement therapy to manage vasomotor symptoms, including hot flashes, is contraindicated in patients with hormone sensitive tumours because of the increased risk of disease recurrence or progression. Although a recently approved non-hormonal therapy for treatment of hot flashes is available, it is advised that due to a potential for interference with tamoxifen metabolism it should not be used in patients on tamoxifen therapy.

 

A non-hormonal treatment for hot flashes resulting from breast cancer therapy is urgently needed.

Clinical trials to date

To date Q-122 has now been safely administered to a total of 62 participants in 4 separate clinical trials as described briefly below.

  • Phase 1 - first-in-human (FIH) study:  Examined the safety of Q-122 in cancer patients with solid or haematological malignancies In this study, seven cancer patients received either 50 or 75 mg of Q-122 daily for up to 110 days. No maximum tolerated dose was identified, and no trends in adverse events (AEs) noted.

  • Phase 1 Single Ascending Dose (SAD):  In this study, 22 healthy participants received single doses of 50 mg, 100 mg, 200 mg or 400 mg Q-122.  Q-122 was well tolerated with no serious adverse events (SAEs) reported. 

  • Phase 1b Initial Proof-of-Concept (Q-1001):  This open-label study enrolled breast cancer survivors taking endocrine therapy (tamoxifen or an aromatase inhibitor) who were experiencing 49 or more moderate to severe hot flashes per week.   In this study, 21 participants received daily doses of 100 mg (10 participants) or 200 mg (11 participants) Q-122 for up to 28 days.  In this study, both the frequency and severity of hot flashes were significantly reduced following treatment with Q-122 as were menopausal symptoms assessed using the Greene Climacteric Scale.

  • Phase 1 Pharmacokinetic (PK) Study (Q122-1002):  A Phase 1 study was conducted to determine the effect of food and dosing regimen on Q-122 pharmacokinetics. In Part 1, healthy volunteers were administered Q-122 (200 mg) in either fed or fasted conditions.  The results demonstrated an increase in bioavailability of Q-122 under fed dosing conditions.  In Part 2, the same 12 participants were randomized to a once daily (200 mg) versus twice daily (2 doses of 100 mg) to examine the effect of the dosing regimen of Q-122.

 

Given these very encouraging study outcomes, QUE has accelerated development of Q-122 as a treatment for vasomotor symptoms in breast cancer survivors taking tamoxifen or an aromatase inhibitor.

 

QUE has commenced a new study – Q122-2001 – “A Randomized, Double Blind, Placebo-Controlled Study of the Safety and Efficacy of Q-122 for the Treatment of Vasomotor Symptoms in Female Breast Cancer Patients/Survivors taking Tamoxifen or an Aromatase Inhibitor. The multi-centre study is currently recruiting breast cancer patients and survivors in Australia, New Zealand and the United States of America.