A Study Of Oral Palbociclib (PD-0332991), A CDK4/6 Inhibitor, As Single Agent In Japanese Patients With Advanced Solid Tumors Or In Combination With Letrozole For The First-Line Treatment Of Postmenopausal Japanese Patients With ER (+) HER2 (-) Advanced Breast Cancer

• Neoplasms
• Breast Neoplasms

• Drug: PD-0332991
  PD-0332991 (100 mg or 125 mg) will be orally administered once a day for 3 weeks followed by 1 week off treatment, in the morning on an empty stomach. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.
• Drug: PD-0332991
  PD-0332991, 125 mg, will be orally administered with food once a day for 3 weeks followed by 1 week off treatment. PD-0332991 will be administered once a day together with letrozole. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.
• Drug: letrozole
  Letrozole, 2.5 mg, will be orally administered once a day in continuous daily dosing together with PD-0332991. Dose reduction of letrozole is not permitted, but dosing interruptions for letrozole-related toxicity are allowed as per investigator's medical judgement.

• Experimental: Single-agent PD-0332991
  Phase 1 Part 1
  Intervention: Drug: PD-0332991
• Experimental: PD-0332991 in combination with letrozole
  Phase 1 Part 2
  Interventions:

  • Drug: PD-0332991
  • Drug: letrozole
• Experimental: PD-0332991 with letrozole
  Phase 2
  Interventions:

  • Drug: PD-0332991
  • Drug: letrozole

• Takahashi M, Masuda N, Nishimura R, Inoue K, Ohno S, Iwata H, Hashigaki S, Muramatsu Y, Umeyama Y, Toi M. Palbociclib-letrozole as first-line treatment for advanced breast cancer: Updated results from a Japanese phase 2 study. Cancer Med. 2020 Jul;9(14):4929-4940. doi: 10.1002/cam4.3091. Epub 2020 May 18.
• Masuda N, Mukai H, Inoue K, Rai Y, Ohno S, Mori Y, Hashigaki S, Muramatsu Y, Umeyama Y, Iwata H, Toi M. Neutropenia management with palbociclib in Japanese patients with advanced breast cancer. Breast Cancer. 2019 Sep;26(5):637-650. doi: 10.1007/s12282-019-00970-7. Epub 2019 May 24. Erratum in: Breast Cancer. 2019 Jun 5;:.
• Tamura K, Mukai H, Naito Y, Yonemori K, Kodaira M, Tanabe Y, Yamamoto N, Osera S, Sasaki M, Mori Y, Hashigaki S, Nagasawa T, Umeyama Y, Yoshino T. Phase I study of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, in Japanese patients. Cancer Sci. 2016 Jun;107(6):755-63. doi: 10.1111/cas.12932. Epub 2016 May 11.

Inclusion Criteria:

Phase 1

• In Part 1, advanced solid tumor (except SCLC or retinoblastoma) proven histologically or cytologically at original diagnosis, that is refractory to standard therapy or for whom no standard of care therapy is available.
• In Part 2 and Phase 2, post menopausal women with proven diagnosis of ER-positive, HER2-negative adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease (including bone only disease) not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated.
• Adequate blood cell counts, kidney function and liver function and and Eastern Cooperative Oncology Group [ECOG] score of 0 or 1.
• Resolved acute effects of any prior therapy to baseline severity or Grade ?1

Phase 2

• Adult women (? 20 years of age) with proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated.
• Documentation of histologically or cytologically confirmed diagnosis of ER(+) breast cancer based on local laboratory results.
• Adequate blood cell counts, kidney function and liver function and and Eastern Cooperative Oncology Group [ECOG] score of 0 to 2.

Exclusion Criteria:

Phase 1

• Active uncontrolled or symptomatic CNS metastases.
• Uncontrolled infection, unstable or sever intercurrent medical condition, or current drug or alcohol abuse
• Active or unstable cardiac disease or history of heart attack within 6 months

Phase 2

• HER2 positive tumor based on local laboratory results utilizing one of the sponsor approved assays.
• Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease.
• Prior neoadjuvant or adjuvant treatment with a non steroidal aromatase inhibitor (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment.