Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Key Inclusion Criteria
Patient has ECOG performance status of 0-1
One or more documented primary oncogenic PIK3CA mutation(s) in blood and/or tumor per
local assessment
- Other potentially oncogenic PIK3CA mutations may be considered but must be approved
by the Sponsor prior to enrollment.
Part 1 - Ability to provide archived tumor tissue or be willing to undergo pretreatment
tumor biopsy to assess PIK3CA status retrospectively Part 2 - Submit tumor tissue prior
to study drug initiation for determination of PIK3CA mutation retrospectively.
Key Inclusion for RLY-2608 Single Agent Arm
- [For Part 1]: Evaluable disease per RECIST v1.1
- [For Part 2]: Measurable disease per RECIST v1.1
- Disease that is refractory to standard therapy, intolerant to standard therapy, or
has declined standard therapy.
- Part 1- histologically or cytologically confirmed diagnosis of unresectable or
metastatic solid tumor
- Part 2 - Unresectable or metastatic solid tumor with PIK3CA mutation(s) and one of
the following tumor types:
Group 1: clear cell ovarian cancer Group 2: head and neck squamous cell carcinoma Group
3: cervical cancer Group 4: other solid tumors, excluding colorectal, clear cell ovarian,
head and neck squamous cell, and cervical cancers Group 5: unresectable or metastatic
solid tumors with PIK3CA double mutations In addition, the SRC (with Sponsor approval)
may choose to open additional group(s) of 20 participants to study the clinical activity,
safety, and PK/PD in other specified solid tumor types.
Key Inclusion for Combination Arms
- [For Part 1 and Part 2]: Evaluable disease per RECIST v1.1
- [For Part 1 and Part 2]: Male or female with histologically or cytologically
confirmed diagnosis of HR+, HER2- unresectable or metastatic breast cancer that is
not amenable to curative therapy. Females may be postmenopausal, premenopausal, or
perimenopausal. Premenopausal or perimenopausal females must have a histologically
or cytologically confirmed diagnosis of HR+ HER2- advanced or metastatic breast
cancer that is not amenable to curative therapy and must have been previously
treated with GnRH agonist at least 4 weeks prior to start of study drug
- [For Part 1 and Part 2]: Had previous treatment for breast cancer with:
1. ≤1 line of chemotherapy in the metastatic setting
2. ≥1 CDK4/6 inhibitor in either the adjuvant and/or metastatic setting
3. ≥1 antiestrogen therapy in either adjuvant and/or metastatic setting,
including, but not limited to, selective estrogen-receptor degraders (eg,
fulvestrant), selective estrogen receptor modulators (eg, tamoxifen), and
aromatase inhibitors (AI) (letrozole, anastrozole, exemestane), and
4. ≥1 PARP inhibitor, if appropriate, if documented germline BRCA1/2 mutation
Note: Systemic local, loco-regional, or adjuvant treatment with chemotherapy
and PARP inhibitors is not to be included in enumeration or previous treatment
[For RLY-2608 + fulvestrant arm; Part 2, Group 2]: Received prior treatment with a PI3Kα
or AKT inhibitor and discontinued the inhibitor due to intolerance and not disease
progression, where intolerance is defined as treatment discontinuation due to treatment
related AE (eg. hyperglycemia, rash, diarrhea, stomatitis) other than severe
hypersensitivity reaction and/or life-threatening reactions, such as anaphylaxis and
Stevens-Johnson syndrome.
[For triple combination arms; Part 1 only]: Participants who had previous treatment for
breast cancer with PI3Kα or AKT inhibitors will be considered.
[For triple combination arms with ribociclib or palbociclib; Part 1 only]: endometrial
cancer may be enrolled.
Key Exclusion Criteria
Prior treatment with PI3Kα, AKT, or mTOR inhibitors (except for RLY-2608 + fulvestrant
arm, Part 2, Group 2; and triplet combinations, Part 1).
Type 1 or Type 2 diabetes requiring antihyperglycemic medication, or fasting plasma
glucose ≥140 mg/dL and glycosylated hemoglobin (HbA1c) ≥7.0%.
History of hypersensitivity to PI3K inhibitors. For combination arms only:
hypersensitivity to fulvestrant, palbociclib, ribociclib, and/or PF-07220060, as
appropriate for the combination.
Past medical history of or ongoing ILD, or pneumonitis requiring intervention.
Participants with past history of resolved Grade 1 pneumonitis may be considered, except
in triple combination arms.
Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) >470 msec. For triple combination arm with
ribociclib: Mean QTcF ≥450 msec.
- Patient has a history of prolonged QT syndrome or torsades de pointes. Patient has a
familial history of prolonged QT syndrome.
- Clinically significant, uncontrolled cardiovascular disease
CNS metastases or primary CNS tumor that is associated with progressive neurologic
symptoms