HIDDEN GEMS

Question 1

OTHER GYN CANCER TRIALS

NRG-GY025

A Randomized Phase II Trial of Nivolumab and Ipilimumab Compared to Nivolumab Monotherapy in Patients with Deficient Mismatch Repair System Recurrent Endometrial Carcinoma

Schema:

ARM 1 Nivolumab Q3W and Low-Dose Ipilimumab Q6W (every other cycle x 4) and then nivolumab alone Q4W
ARM 2 Nivolumab Q3W x 8 cycles then Q4W

Prior Therapies:
May have received 1-2

Measurable Disease:
No (can have measureable or non measureable)

Answer 1

Inclusion
•Must have MMR testing completed
•Endometrioid adenocarcinoma, mucinous adenocarcinoma, dedifferentiated/undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.).
• ECOG <2

Exclusion

•Endometrial serous carcinoma or carcinosarcoma
• Prior anti-PD1/PD-L1 therapy and had grade 3-4 or recurring grade 2 immune-related toxicities that led to dose delay or discontinuation of immunotherapy due to those toxicities.
• Chronic steroid therapy
• Active autoimmune disease or history of autoimmune disease that might recur

Question 2

PRIMARY OVARIAN CANCER

NRG-GY027

Phase I/IB safety and pharmacodynamic study of neoadjuvant (NACT) paclitaxel and carboplatin with ipatasertib as initial therapy of ovarian cancer

Schema:

Neoadjuvant Chemotherapy (NACT) Paclitaxel/Carboplatin + Ipatasertib po QD Q3W x 3 cycles
Followed by single-agent ipatasertib daily until 24 hours prior to Interval Debulking Surgery (IDS)

Prior Therapies:
None

Measurable Disease:
Yes RECIST 1.1

Answer 2

Inclusion:
Pathologically proven diagnosis of ovarian cancer stage III or IV
a. High grade serous
b. Endometrioid adenocarcinoma, grade 3
• NACT patients only
•ECOG <2
•HIV, HBV and HCV eligible if undetectable viral
load

Exclusion:
•Prior tx with P13K/AKT/Mtor pathway
• GI obstruction or bleeding within 6 months
• Prior radiotherapy to abdomen
• active infection involving IV atibiotics
• Pt on insulin therapy or baseline fasting glucose >160mg/dl or HbA1c >8
• > Grade 2 uncontrolled hypercholesterolemia (>300 mg/Dl) or triglycerides >300 mg/Dl)
• hx active inflammatory bowel disease
• Lung disease
• Brain mets
• Tx with strong CyP3a inhibitors

Question 3

RECURRENT PLATINUM SENSITIVE OVARIAN CANCER

GOG 3049 (UP NEXT)

Phase 3 Study of UpRi Monotherapy
Maintenance vs Placebo in Platinum-Sensitive Recurrent OC

Schema:
XMT-1536 (upifitamab rilsodotin) IV Q4W

Prior Therapies:
• 2–4 prior platinum-based regimes
(including induction)
• Prior PARPi therapy allowed, but only
required for BRCAmut

Measurable Disease:
YES RECIST 1.1

Answer 3

Inclusion:
• Platinum-sensitive recurrence (after PR or CR)
• High grade serous histology
• Archived tumor and fresh biopsy (if medically feasible) for NaPi2b
• Must have BRCA testing completed

Exclusion:
Primary platinum-resistant
• Received prior treatment with mirvetuximab soravtansine
• Received bevacizumab in combination with last platinum-based regiment or plans to receive maintenance therapy outside the study intervention.
• S/S of gastrointestinal obstruction and/or requirement for parenteral hydration or nutrition.
• Ascites or pleural effusion
• Hx of cirrhosis, hepatic fibrosis, esophageal or gastric varices, or other clinically significant liver disease.
• Hx of or suspected pneumonitis or interstitial lung disease.
• Untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis, or carcinomatous meningitis.

Question 4

RECURRENT PLATINUM SENSITIVE OVARIAN CANCER

GOG 3072

A PHASE 1b STUDY OF ZN-c3 IN
COMBINATION WITH CHEMOTHERAPY IN
PATIENTS WITH PLATINUM-RESISTANT
OVARIAN, PERITONEAL,
OR FALLOPIAN TUBE CANCER

Schema:
ZN-c3 + PLD
ZN-c3 + Carboplatin
ZN-c3 + Paclitaxel
ZN-c3 + Gemcitabine

Prior Therapies:
1-2 prior lines (1 prior line MUST have contained cisplatin or carboplatin

Measurable Disease:
YES RECIST 1.1

Answer 4

Inclusion:
Platinum refractory or resistant
• High-grade serous epithelial ovarian carcinoma, fallopian tube, or peritoneal carcinoma
•Adequate hematologic and organ function
negative serum beta human chorionic gonadotropin (β-hCG) test.
•Left ventricular ejection fraction (LVEF) ≥50% or within normal limits of the institution (only for subjects treated with PLD).

Exclusion:
• Histology of abdominal adenocarcinoma of unknown origin or diagnosis of a borderline ovarian tumor
• Radiation therapy within 21 days
• Brain metastases that require immediate treatment or are clinically or radiologically unstable
• Myocardial impairment of any cause
• Significant gastrointestinal abnormalities
• Active or uncontrolled infection.
• Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia or skin pigmentation).
• Subjects with active (uncontrolled, metastatic) second malignancies