A Phase I/IIa Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-Tumor Activity of PF-07220060 as a Single Agent and as Part of Combination Therapy in Participants With Advanced Solid Tumors
Study Identifier:
C4391001
CT.gov Identifier:
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
Study Contact Information:
N/A
Recruitment Complete
Considering participating in a START clinical trial?
Study Summary
To evaluate safety, tolerability, pharmacokinetic and pharmacodynamic study of PF-07220060 administered as a single agent and then in combination with endocrine therapy.
Part 1A
To determine the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D) in single escalating doses of PF-07220060 alone
Part 1B and Part 1C:
To determine the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D of PF-07220060 in combination with 1 of 2 endocrine therapies (letrozole and fulvestrant, respectively).
Part 1D: Evaluate the effect of food on PK and safety and tolerability when PF-07220060 monotherapy RP2D and/or RDE is administered. Part 1E: Evaluate the effect of repeated administration of PF-07220060 RP2D and/or RDE on the PK of a single dose of oral midazolam; safety and tolerability of monotherapy RP2D and/or RDE. Part 1F: In mCRPC study participants Evaluate the safety and tolerability of PF-07220060 in combination with enzalutamide to estimate the MTD and select the RP2D and/or RDE for this combination. Part 2A, 2B, 2C and 2E: Further evaluate the safety and tolerability of PF-07220060 in combination with the following drugs. Part 2A, 2B and 2C: Combined with letrozole or fulvestrant at the selected RP2D and/or RDE in patients with HR+HER2-advanced or mBC. Part 2E: Further evaluate the safety and tolerability of monotherapy and combination with fulvestrant at the selected RP2D and/or RDE in patients with HR+HER2-advanced or mBC. Chinese Monotherapy Cohort: Evaluate the PK of single-dose and multiple-dose administration of PF-07220060.
Mean variant allele frequency (meanVAF) was used to determine the ctDNA molecular response (MR) between timepoints.
To present the efficacy and safety results from an expansion cohort in the phase 1/2a study of atirmociclib in combination with
letrozole in treatment-naïve patients with HR+/HER2– mBC (cohort 2B).
To evaluate PF-07220060 + enzalutamide in Patients with Prostate Cancer
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
18+ years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Recruitment Complete
Requirements information
Inclusion criteria
- Part 1: Breast Cancer (BC)
- Refractory Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) BC
- Part 1A/Part 1D/Part1E also include: Refractory HR-positive/HER2-positive BC
- Part 1: Tumors other than BC (Part 1A/Part 1D/Part 1E): NSCLC, prostate, CRC, liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according to local standard tests
- Part 1F: prostate cancer
- Part 2A, 2B and 2C:
- HR-positive/HER2-negative BC
- Patients who are either postmenopausal women or pre/peri-menopausal (Part 2C only)
- Part 1D: metastatic castration resistant prostate cancer
- Lesion:
- Part 1: evaluable lesion (including skin or bone lesion only)
- Part 2A, 2B and 2C: measurable lesion per RECIST v1.1
- Part 2D: Participants with evaluable disease as per PCWG3; participants with bone metastases only are allowed. Participants with biochemical recurrence only are excluded.
- Prior systemic Treatment
- Part 1: HR-positive/HER2-negative BC
- At least 1 line of SOC, including CD4/6 inhibitor therapy for advanced or metastatic disease, or if CDK4/6 inhibitors are not considered appropriate in the opinion of the investigator
- At least 1 line of anti-endocrine in countries without CDK4/6 inhibitor approval or reimbursement, for advanced or metastatic disease
- HR-positive/HER2-positive BC (Parts 1A/1D/1E): at least 1 prior treatment of approved HER2 targeting therapy
- Tumors other than BC (Parts 1A/1D/1E/1F): tumor that is resistant to at least 2 lines of SOC for advanced or recurrent disease or for which no standard therapy is available
- Part 2A: participants must have received at least 1 line of standard of care (including prior CDK4/6i) for advanced/metastatic disease; Prior chemo is allowed; Prior fulvestrant, mTOR and/or PI3K inhibitors are allowed
- Part 2B: participants who have not received any prior systemic anti-cancer therapies for advanced/metastatic BC
- Part 2C:
- Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre or perimenopausal, or
- Progressed while on or within 1 month after the endo the prior aromatase inhibitor therapy for advanced/metastatic BC if postmenopausal or prior endocrine treatment for advanced/metastatic BC if pre or perimenopausal
- One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy
- Part 2D:
- Received prior abiraterone; enzalutamide and CDK4i naive
- 0-1 line of chemotherapy is allowed General Inclusion Criteria
- All participants must be refractory to or intolerant of existing therapies known to provide clinical benefit for their condition.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
- Adequate renal, liver, and bone marrow function
- Per CFDA
- Parts 1B and 1C: Refractory HR-positive/HER2-negative (second-line and later populations previously treated with CDK4/6) breast cancer. b. Parts 1A, 1D, and 1E will include the above requirements plus: Refractory HR-positive/HER2-positive breast cancer; Tumors other than BC: NSCLC, prostate cancer, CRC, liposarcoma, or tumors with previous confirmation of CDK4 or CCND1 amplification by local standard testing c. Part 1F: Histological or cytological diagnosis of prostate cancer with progression after previous line therapy according to PCWG3.
- 2 Parts 2A, 2B, 2C, and 2D: HR-positive/HER2-negative breast cancer Part 2D: Castration-resistant prostate cancer diagnosed by histology or cytology and progressing after prior therapy according to PCWG3.
- 3 Chinese Monotherapy Cohort: 1. Subjects with histologically or cytologically confirmed breast cancer and locally advanced or metastatic breast cancer that cannot be removed or cured by radiotherapy: a. HR-positive/HER2-negative breast cancer. b. HR-positive/HER2-positive breast cancer. 2. Patients aged ≥18 years (female and male): Female subjects with HR-positive, HER2-negative advanced or metastatic BC who are of childbearing potential (or have only undergone tubal ligation) must be willing to undergo medically induced menopause using the LHRH agonist goserelin, the gonadotropin-releasing hormone (GnRH) agonist leuprorelin (Lupron Depot®), or an equivalent drug that induces chemical menopause.
- 4 Lesion requirements: a. For Part 1 and the Chinese monotherapy cohort: must have evaluable lesions (including skin lesions or bone metastases only). b. For Parts 2A, 2B, 2C, and 2E: must have measurable lesions as defined by RECIST version 1.1. For tumor lesions that have been previously treated with radiotherapy or local therapy, they are considered measurable lesions only if progression at the treatment site has been clearly documented after completion of treatment. c. For Part 2D: Subjects have evaluable lesions according to PCWG3. Patients with bone metastases only are allowed to enroll. Patients with only biochemical recurrence are excluded.
- 5 Prior systemic therapy: a. Part 1: HR-positive/HER2-negative breast cancer (Part 1A/Part 1B/Part 1C/Part 1D/Part 1E): Study participants should have received the following treatments: At least 1 line of SOC for advanced or metastatic disease, including CDK4/6 inhibitor therapy, or, if a CDK4/6 inhibitor is available but deemed unsuitable by the investigator, they may be enrolled after the investigator provides a compelling clinical rationale and obtains approval from the sponsor. Or 1) At least 1 line of anti-endocrine therapy for advanced or metastatic disease in countries where CDK4/6 inhibitors are not approved or reimbursed. 2) Part 1C subjects whose last prior therapy included fulvestrant are eligible to participate. See Section 6.1.1.3. In both cases, prior chemotherapy for advanced disease is allowed.
- 6 Previous systemic therapy: b. Part 2: Part 2A and 2E: 1) Study participants must have received at least 1 line of SOC for advanced/metastatic breast cancer, including previous CDK4/6 inhibitor therapy. 2) Previous chemotherapy for advanced disease is allowed. 3) Previous treatment with fulvestrant, mTOR and/or PI3K inhibitors is allowed. Part 2B: Subjects who have not received any previous systemic anticancer therapy for advanced/metastatic breast cancer Part 2C: 1) Progression during or within 12 months after completion of adjuvant therapy with aromatase inhibitors (postmenopausal patients) or tamoxifen (premenopausal or perimenopausal patients), or 2) Progression during or within 1 month after completion of previous aromatase inhibitor therapy for advanced/metastatic breast cancer (postmenopausal patients), or progression during or within 1 month after completion of previous endocrine therapy for advanced/metastatic breast cancer (premenopausal or perimenopausal patients). 3) In addition to endocrine therapy, previous first-line chemotherapy for advanced/metastatic disease was also allowed.
- 7 Previous systemic therapy: Part 2D: 1) Previously treated with abiraterone for any disease. Note: Unless bilateral orchiectomy is performed, maintenance LHRH agonist or antagonist therapy is required. 2) Not treated with enzalutamide, apalutamide, darolutamide, and CDK4/6 inhibitors. 3) Previously received up to 1 line of chemotherapy for any disease stage.
- 8 Prior systemic therapy: Chinese monotherapy cohort 1) HR-positive/HER2-negative breast cancer: Study participants had previously received at least 1 line of standard endocrine therapy (with or without CDK4/6 inhibitors) for locally advanced or metastatic disease 2) HR-positive/HER2-positive breast cancer: Study participants should have received at least one approved HER2-targeted therapy for locally advanced or metastatic disease. 3) In both cases, prior chemotherapy for advanced disease was allowed.
- 9 All subjects: Patients with locally advanced or metastatic solid tumors confirmed by histology or cytology, and whose tumors cannot be removed or irradiated for curative purposes.
- 10 General Inclusion Criteria1) Subjects in Part 1, Part 2 (except Part 2B and Part 2D) and the Chinese monotherapy cohort must be refractory or intolerant to existing treatments known to provide clinical benefit for their condition. 2) Subjects must be ≥18 years old. 3) ECOG PS is 0 or 1. 4) Have adequate bone marrow function, adequate renal function, and adequate liver function. 5) Any acute effects of previous treatment have resolved to baseline severity or CTCAE ≤1, except for AEs that the investigator determines do not pose a safety risk. 6) Willing and able to follow scheduled visits, treatment plans, laboratory tests, and other procedures. 7) Able to sign the informed consent described in the protocol, including compliance with the requirements and restrictions listed in the informed consent form and protocol. 8) Any postmenopausal woman is allowed to enroll in the study; however, non-postmenopausal women can be enrolled if they are suitable for treatment with the LHRH agonist goserelin. Patients must have started treatment with goserelin or other LHRH agonists for at least 4 weeks before enrollment.
- Per EUCT
- Disease requirements for Part 1 a. Part 1B and Part 1C: - Refractory HR-positive/HER2-negative (2L+ with prior CDK4/6) breast cancer. b. Part 1A, Part 1D and Part 1E will include the above and: Refractory HR-positive/HER2-positive breast cancer. Tumors other than BC: NSCLC, prostate, CRC, liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according to local standard tests c. Part 1F: - Histological or cytological diagnosis of prostate cancer that has progressed from last therapy as per PCWG3.
- Adequate liver function, as evidenced by: a. Total serum bilirubin ≤1.5 × ULN unless the participant has documented Gilbert syndrome (in which case, up to total serum bilirubin ≤3.0 × ULN will be allowed); b. AST and ALT ≤2.5 × ULN; ≤5.0 × ULN if there is liver involvement by the tumor; c. ALKP ≤2.5 × ULN (≤5.0 × ULN in case of bone or liver metastasis).
- Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1 except for AEs not constituting a safety risk as determined by the investigator.
- Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.
- Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
- Women of any menopausal status are allowed; however, women who are not considered post-menopausal are allowed to enroll if amenable to be treated with the LHRH agonist goserelin. Patients must have commenced treatment with goserelin or an alternative LHRH agonist at least 4 weeks prior to enrollment. If patients have received an alternative LHRH agonist prior to study entry, it is preferable to switch to goserelin for the duration of the trial. However other LHRH antagonists, such as leuprolide is acceptable.
- Disease requirements for Part 2 Part 2A, 2B and Part 2C: a. HR-positive/HER2-negative breast cancer Part 2D: Histological or cytological diagnosis of castration resistant prostate cancer that has progressed from last therapy as per PCWG3.
- Lesion requirements a. For Part 1: participant must have evaluable lesion (including skin or bone lesion only). b. For Part 2A, 2B and Part 2C: participants must have measurable disease as defined per RECIST version 1.1. Tumor lesions previously irradiated or subjected to locoregional therapy will only be deemed measurable if progression at the treated site after completion of therapy is clearly documented. c. For Part 2D: Participants with evaluable disease by PCWG3. Participants with bone metastases only are allowed. Participants with biochemical recurrence only are excluded.
- Prior Systemic Treatment: a. For Part 1: •HR-positive/HER2-negative Breast Cancer (Part 1A/Part 1B/Part 1C/ Part 1D/Part 1E): •Participants should have received: •at least 1 line of SOC, including CDK4/6 inhibitor therapy for advanced or metastatic disease, or if CDK4/6 inhibitors are available but not considered appropriate in the opinion of the investigator, participants may be enrolled if a compelling clinical rationale is provided by the investigator and approved by the sponsor. or •at least 1 line of anti-endocrine therapy in countries without CDK4/6 inhibitor approval or reimbursement, for advanced or metastatic disease. •Participants in Part 1C who received fulvestrant as part of the last prior therapy are eligible. See Section 6.1.1.3. Prior chemotherapies for advanced disease setting are allowed in both cases. •HR-positive/HER2-positive Breast Cancer (Part 1A/Part 1D/Part 1E): Participants should have received at least one prior treatment of approved HER2 targeting therapy. •Tumors Other Than Breast Cancer (Part 1A/Part 1D/Part 1E): tumor that is resistant to at least 2 lines of standard systemic therapy for advanced or recurrent disease or for which no standard therapy is available. For Part 1F: tumor that is resistant to at least 1 line of standard systemic therapy for advanced or recurrent disease or for which no standard therapy is available. Note: Maintenance with LHRH agonist or antagonist is permitted. b. For Part 2: Part 2A: •Participants must have received at least 1 line of SOC, including prior CDK4/6 inhibitor, for advanced/metastatic breast cancer. •Prior chemotherapies for advanced disease setting are allowed. •Prior fulvestrant, mTOR and/or PI3K inhibitors are allowed. Part 2B: •Participants who have not received any prior systemic anti-cancer therapies for advanced/metastatic breast cancer. Part 2C: •Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre-or perimenopausal, or •Progressed while on or within 1 month after the end of prior aromatase inhibitor therapy for advanced/metastatic breast cancer if postmenopausal, or prior endocrine treatment for advanced/metastatic breast cancer if pre- or perimenopausal. •One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy. Part 2D: •Received prior treatment with abiraterone in any setting. Note: Maintenance of LHRH agonist or antagonist is required unless treated with bilateral orchiectomy. •Enzalutamide, apalutamide-, darolutamide- and CDK4/6- inhibitor naïve. •Up to 1 prior line of chemotherapy in any setting.
- General Inclusion Criteria 1. Participants in both Part 1 and Part 2 (except for Part 2B and Part 2D) must be refractory to or intolerant of existing therapies known to provide clinical benefit for their condition.
- Participants age ≥18 years (all parts).
- ECOG PS of 0 or 1.
- Adequate bone marrow function, as evidenced by: a. ANC ≥1,500/mm3 or ≥1.5 x 109/L; b. platelets ≥100,000/mm3 or ≥100 x 109/L; c. hemoglobin ≥9 g/dL. Limited transfusions to reach this value are allowed, after discussion with sponsor’s medical monitor. There should not be a chronic need for transfusions in the recent past (approximately 3 months).
- Adequate renal function, defined as: a. estimated creatinine clearance ≥50 mL/min for Part 1 as calculated using the method standard for the institution. In equivocal cases, a 24-hour urine collection test may be used to estimate the creatinine clearance more accurately.
Exclusion criteria
- Part 1D: participants who have had a gastrectomy or have dietary or other restrictions that preclude a 10 hour overnight fast or consumption of the high fat, high calorie meal
- Part 2B: prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor with disease recurrence while on or within 12 months of completing treatment. Prior treatment with any CDK4/6 inhibitor
- Part 2C: prior treatment with any CDK inhibitor, fulvestrant, everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway
- Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases carcinomatous meningitis, or leptomeningeal disease
- Other active malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
- Major surgery or radiation within 4 weeks prior to study intervention
- Last anti-cancer treatment within 2 weeks prior to study intervention
- Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry
- Pregnant or breastfeeding female participant
- Active inflammatory gastrointestinal (GI) disease, known diverticular disease or previous gastric resection or lap band surgery including impairment of gastrointestinal function or GI disease
- Per CFDA
- Part 1D only: Study participants who have undergone gastrectomy or have dietary or other restrictions that prevent an overnight 10-hour fast (water allowed) or consumption of a high-fat, high-calorie meal.
- 2 For Part 2B, - Prior neoadjuvant or adjuvant treatment with a nonsteroidal aromatase inhibitor (i.e., anastrozole or letrozole) with disease recurrence during treatment or within 12 months after completion of treatment. - Prior treatment with any CDK4/6 inhibitor
- 3 For Part 2C only: Prior treatment with any CDK inhibitor, or fulvestrant, or everolimus, or any agent that inhibits the PI3K-mTOR pathway
- 4 Known uncontrolled active or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease based on clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or spinal cord compression who have been clinically stable without anticonvulsants and steroids for at least 4 weeks prior to enrollment after receiving definitive treatment (e.g., radiation therapy, stereotactic surgery) and have no evidence of disease progression at study enrollment may also participate in the study
- 5 Patients with advanced/metastatic, symptomatic, visceral metastases who may experience life-threatening complications in the short term (including patients with large uncontrolled effusions [pleural, pericardial, peritoneal], subjects with pulmonary lymphangitis, and patients with greater than 50% liver involvement).
- 6 Any other active malignancy within 3 years before enrollment, except for adequately treated basal cell or squamous cell skin cancer or carcinoma in situ.
- 7 Major surgery within 4 weeks before study entry.
- 8 Radiation therapy (RT) with curative intent within 4 weeks prior to study entry. Any palliative RT must have been completed within 7 days prior to Day 1 of study treatment intervention.
- 9 Participants whose last treatment was enzalutamide or apalutamide should have received their last anticancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to the study treatment intervention, or 4 weeks or 5 half-lives (whichever is shorter) if their last direct anticancer treatment consisted of an antibody (approved or investigational). Part 1F: For participants whose last treatment was enzalutamide or apalutamide, the washout period should be at least 24 days.
- 10 Participation in other studies involving investigational medicinal products within 4 weeks or 5 half-lives (whichever is shorter) prior to study entry.
- 11 Have received high-dose chemotherapy requiring stem cell rescue.
- 12 Active and clinically significant bacterial, fungal or viral infection, including but not limited to HBV, HCV, known HIV or AIDS-related illness. In equivocal cases with positive serology, subjects with negative viral load may be eligible for the study, provided that other inclusion criteria are met (see Table 1).
- 13 Baseline 12-lead ECG shows clinically relevant abnormal results that may affect subject safety or interpretation of study results. If the baseline uncorrected QT interval is >470 msec, the interval should be corrected for heart rate using the Fridericia method, and the decision and reporting should be based on the QTcF result obtained. If the QTc exceeds 470 msec or the QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the 3 QTc or QRS values should be taken to determine the eligibility of the subject. Before excluding a subject, the computer-interpreted ECG should be read through by a physician with experience in ECG reading. The case must be discussed in detail with the sponsor's medical monitor to determine eligibility.
- 14 Any of the following within the past 6 months: myocardial infarction, congenital long QT syndrome, torsades de pointes, arrhythmia, severe conduction system abnormalities, unstable angina, coronary artery/peripheral artery bypass grafting, symptomatic CHF, New York Heart Association class III or IV, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism; deep vein thrombosis; arterial occlusive disease; sustained arrhythmia of NCI CTCAE grade ≥2, uncontrolled atrial fibrillation of any grade, or QTcF interval >470 msec at screening.
- 15 Uncontrolled blood pressure (≥150/90 mmHg despite optimal medical therapy).
- 16 Therapeutic doses of anticoagulants are strictly prohibited (prophylactic doses of anticoagulants are permitted)
- 17 Known coagulation disorder, such as a bleeding diathesis
- 18 Known or suspected hypersensitivity to the active ingredients/excipients of PF-07220060, letrozole, fulvestrant, and/or goserelin (or equivalent agents for inducing chemical menopause).
- 19 Active inflammatory gastrointestinal disease, known diverticular disease or previous gastrectomy or banding. Gastrointestinal impairment or disease that could significantly alter the absorption of PF-07220060, such as a history of gastrointestinal surgery that may result in small bowel blind loop syndrome and clinically significant gastroparesis, short bowel syndrome, unrelieved nausea, vomiting, active inflammatory bowel disease, or CTCAE grade >1 diarrhea.
- 20 The patient is currently taking any medications that carry a risk of QTc prolongation (see Appendix 7 of the protocol).
- twenty one Foods or drugs known to be strong CYP3A4/5 or UGT2B7 inhibitors are being used or are expected to be used, including use within 5 half-lives of CYP3A4/5 or UGT2B7 inhibitors before the first dose of the study drug. Moderate CYP3A4/5 or UGT2B7 inhibitors should be avoided or expected to be used (including use within 5 half-lives of CYP3A4/5 or UGT2B7 inhibitors before the first dose of the study treatment intervention) whenever possible, and any use requires review and approval by the sponsor.
- twenty two Currently taking or anticipating the need for use of medications known to be strong CYP3A4/5 or UGT2B7 inducers, including use within 10 days prior to the first dose of study treatment intervention or within 5 half-lives of the CYP3A4/5 or UGT2B7 inducer, whichever is longer.
- twenty three Use or anticipated need for proton pump inhibitors (PPIs) within 14 days prior to the first dose of study treatment intervention.
- twenty four Other medical or psychiatric conditions that may increase the risk of study participation or (in the investigator's judgment) may make the subject unsuitable for study participation, including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormalities.
- 25 Site personnel or Pfizer employees directly involved in the conduct of the study, site personnel otherwise supervised by the investigator, and their respective family members.
- 26 WOCBP who is currently pregnant or breastfeeding.
- 27 Parts 1F and 2D: Last antihormonal therapy occurred within 2 weeks prior to Cycle 1 Day 1, except for mCRPC study participants who must (unless they have undergone bilateral orchiectomy) maintain an LHRH agonist or antagonist.
- Per EUCT:
- Disease requirements for Part 1 a. Part 1B and Part 1C: - Refractory HR-positive/HER2-negative (2L+ with prior CDK4/6) breast cancer. b. Part 1A, Part 1D and Part 1E will include the above and: Refractory HR-positive/HER2-positive breast cancer. Tumors other than BC: NSCLC, prostate, CRC, liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according to local standard tests c. Part 1F: - Histological or cytological diagnosis of prostate cancer that has progressed from last therapy as per PCWG3.
- Adequate liver function, as evidenced by: a. Total serum bilirubin ≤1.5 × ULN unless the participant has documented Gilbert syndrome (in which case, up to total serum bilirubin ≤3.0 × ULN will be allowed); b. AST and ALT ≤2.5 × ULN; ≤5.0 × ULN if there is liver involvement by the tumor; c. ALKP ≤2.5 × ULN (≤5.0 × ULN in case of bone or liver metastasis).
- Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1 except for AEs not constituting a safety risk as determined by the investigator.
- Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
- Women of any menopausal status are allowed; however, women who are not considered post-menopausal are allowed to enroll if amenable to be treated with the LHRH agonist goserelin. Patients must have commenced treatment with goserelin or an alternative LHRH agonist at least 4 weeks prior to enrollment. If patients have received an alternative LHRH agonist prior to study entry, it is preferable to switch to goserelin for the duration of the trial. However other LHRH antagonists, such as leuprolide is acceptable.
- Disease requirements for Part 2 Part 2A, 2B and Part 2C: a. HR-positive/HER2-negative breast cancer Part 2D: Histological or cytological diagnosis of castration resistant prostate cancer that has progressed from last therapy as per PCWG3.
- Lesion requirements a. For Part 1: participant must have evaluable lesion (including skin or bone lesion only). b. For Part 2A, 2B and Part 2C: participants must have measurable disease as defined per RECIST version 1.1. Tumor lesions previously irradiated or subjected to locoregional therapy will only be deemed measurable if progression at the treated site after completion of therapy is clearly documented. c. For Part 2D: Participants with evaluable disease by PCWG3. Participants with bone metastases only are allowed. Participants with biochemical recurrence only are excluded.
- Is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Midwest
Grand Rapids, MI, United States, 49546
Investigator
Manish Sharma
Status
Recruiting
Condition(s) Treated at Site
Soft Tissue Sarcoma
Prostate
Breast Cancers
Non-Small Cell Lung Cancer