G1T38-02_Phase 1/2 Safety & PK Study of G1T38_Breast Cancer_3652/0002

• Research type

  Research Study

• Full title

  Phase 1/2 Safety, Pharmacokinetic, and Antitumor Activity Study of G1T38 in Combination with Fulvestrant in Patients with Hormone Receptor-Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer after Endocrine Failure

• IRAS ID

  211245

• Contact name

  Rebecca Roylance

• Contact email

  roylance@ucl.ac.uk

• Sponsor organisation

  G1 Therapeutics, Inc

• Eudract number

  2016-001485-29

• Duration of Study in the UK

  years, 35 months, days

• Research summary

  Research Summary:

  This is a phase 1/2, multicentre, open label study to investigate the safety, and effect of G1T38 on patients with breast cancer when used in combination with Fulvestrant and to investigate level of G1T38 in the blood during treatment.

  The study consists of 2 parts. Part 1 will evaluate escalating doses of G1T38 (with Food) in combination with fixed-dose fulvestrant to determine the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D); and Part 2 will be an expansion portion to further evaluate the safety and anti-tumour activity of the MTD/RP2D. Both parts of the study include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow up Phase. The Treatment Phase begins on the day of the first dose of study treatment and completes at the Post Treatment Visit.

  The total study duration is at least 35 months. Part 1 is expected to be approximately 14 months from first patient enrolled until the identification of the Phase 2 dose. This is assuming 6 dose cohorts are investigated, with 4 weeks for enrollment per cohort, assessment of DLTs from the first 4 weeks of treatment, and a dose escalation meeting conducted within 1 week of the last patient completing treatment through week 4.

  Part 2 will begin after the Phase 2 dose is identified from Part 1 and is expected to be approximately 20 months, assuming 10 months of enrollment, approximately 10 months of dosing and 1 month of safety follow-up. The Survival Follow-up Phase will continue until at least 50% of the patients in Part 2 have died.

  102 patients will be enrolled in the study in up to 20 centers in Europe. In Part 1, up to 72 patients may be enrolled. In Part 2, up to 30 patients may be enrolled.

  Summary of Results:
  The primary goal was to find doses of G1T38 that were safe and tolerated by patients and could be further evaluated. Four patients experienced medical problems during their first month of treatment that stopped them from receiving 28 days of continuous daily doses of G1T38. This included one patient each in the 200 mg once daily, 500 mg once daily, 650 mg once daily, and 200 mg twice daily dose groups. The G1T38 dose selected to be further evaluated was 150 mg twice daily by mouth.
  Overall, G1T38 was not associated with severe medical problems and was considered safe and generally well tolerated by most patients.
  Results of the study also demonstrated some benefit for patients with cancer. In Part 1, 60.7% of patients had stable disease, which means their cancer was no longer growing and in Part 2, 50.0% of patients had stable disease. This stable disease lasted at least 24 weeks.

  Conference Presentations:
  1. Bulat, Iurie, et al. G1T38, an oral CDK4/6 inhibitor, dosed continuously in combination with fulvestrant for HR+ breast cancer: Preliminary phase 1b results. JCO 36, 1061-1061(2018): https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fascopubs.org%252Fdoi%252F10.1200%252FJCO.2018.36.15_suppl.1061%2FNBTI%2F-jK1AQ%2FAQ%2F06a84f09-7d18-4cf8-b3e1-964687d10048%2F2%2Fy1MkvS5qZZ&data=05%7C02%7Charrow.rec%40hra.nhs.uk%7C4a9b6af2b30849adfa4208dc700f890b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638508459232569133%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=1U4Aa0cvHEd3e5J4a0bew1joU9OOIh6QLkN8THJf5CU%3D&reserved=0
  2. Bulat, Iurie, et al. Abstract P1-19-17: Dose escalation and expansion study of lerociclib (G1T38), an oral CDK4/6 inhibitor, dosed with no drug holiday in combination with fulvestrant in patients with HR+/HER2-advanced breast cancer. Cancer Research 80.4_Supplement (2020): P1-19. https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Faacrjournals.org%252Fcancerres%252Farticle%252F80%252F4_Supplement%252FP1-19-17%252F646333%252FAbstract-P1-19-17-Dose-escalation-and-expansion%2FNBTI%2F-jK1AQ%2FAQ%2F06a84f09-7d18-4cf8-b3e1-964687d10048%2F3%2FvDYZWXfh52&data=05%7C02%7Charrow.rec%40hra.nhs.uk%7C4a9b6af2b30849adfa4208dc700f890b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638508459232574560%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=kV2mfcKHT066HLCiUGuAUE2B4KwohljVn7dzGC6ditk%3D&reserved=0
  3. Krastev, B., et al. 278MO cfDNA analysis from phase I/II study of lerociclib (G1T38), a continuously dosed oral CDK4/6 inhibitor, with fulvestrant in HR+/HER2-advanced breast cancer patients. Annals of Oncology 31 (2020): S351-S352. https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fwww.annalsofoncology.org%252Farticle%252FS0923-7534&data=05%7C02%7Charrow.rec%40hra.nhs.uk%7C4a9b6af2b30849adfa4208dc700f890b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638508459232579723%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=lAo%2FTl%2FFTcGEudAc4Kb57NJ6vzmuBD8UQ4I%2BVzsBsEY%3D&reserved=0(20)40376-X%2Ffulltext/NBTI/-jK1AQ/AQ/06a84f09-7d18-4cf8-b3e1-964687d10048/4/TNv-2B_t4y
  4. Bulat, I., et al. 334P Lerociclib (G1T38), a continuously dosed oral CDK4/6 inhibitor, with fulvestrant in HR+/HER2-advanced breast cancer patients: Updated phase II results and dose selection. Annals of Oncology 31 (2020): S380. https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fwww.annalsofoncology.org%252Farticle%252FS0923-7534&data=05%7C02%7Charrow.rec%40hra.nhs.uk%7C4a9b6af2b30849adfa4208dc700f890b%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638508459232584483%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=5IRZ2S2ux8oRLHNr%2Fmj619c6lPQQob4z6uC%2BgpYbnZM%3D&reserved=0(20)40432-6%2Ffulltext/NBTI/-jK1AQ/AQ/06a84f09-7d18-4cf8-b3e1-964687d10048/5/gG6nGThg4d

• REC name

  London - Harrow Research Ethics Committee

• REC reference

  17/LO/0285

• Date of REC Opinion

  21 Mar 2017

• REC opinion

  Further Information Favourable Opinion