Title
Randomized Phase 2/3 Trial of NP-G2-044 Combined with PLD for Treatment of Platinum-Resistant Ovarian Cancer

Description
This is an open-label, Phase 2/3, multicenter, randomized study of NP-G2-044 in combination with PLD vs. PLD alone in participants with PROC. The Phase 2 component of the study includes a safety lead-in dose escalation of NP-G2-044 monotherapy with twice daily (BID) dosing and a dose escalation phase for NP-G2-044+PLD followed by a randomized dose optimization phase of NP-G2-044+PLD compared with PLD. In the Phase 3 component of the study, participants will be randomized to treatment with NP-G2-044+PLD, at the dose selected from the dose optimization phase, or to PLD alone. Randomized participants will be stratified according to the number of prior lines of therapy, number of prior PLD therapy lines, and region of the world. The study population is women at least 18 years of age with confirmed ovarian high grade serous carcinoma, an Eastern Cooperative Oncology Group (ECOG) status of 0-1, and whose cancer is resistant to platinum-based therapy.

Objective
Part A Primary: To assess the safety and tolerability of NP-G2-044 monotherapy with BID dosing and in combination with PLD and to determine the RP2D of NP-G2-044 when combined with PLD
Secondary: To assess the initial efficacy of NP-G2-044 in combination with PLD.
To compare the treatment groups for safety and tolerability.
To compare the treatment groups for participant-reported QoL.
To characterize the PK of NP-G2-044 monotherapy with BID dosing and to characterize the PK of NP-G2-044 and PLD under combination therapy.
Part B Primary: To compare the treatment groups for safety and tolerability.
To identify the optimal dose of NP-G2-044 combined with PLD.
Secondary: To compare the treatment groups for additional efficacy parameters.
To compare the treatment groups for participant-reported QoL.
To characterize the PK of NP-G2-044 and PLD under combination therapy.
Part C (Phase 3) Primary: To compare efficacy of NP-G2-044 when combined
with PLD vs. PLD alone.
Secondary: To compare the treatment groups for additional efficacy endpoints.
To compare the treatment groups for safety and tolerability.
To compare the treatment groups for participant-reported QoL.

Treatment The purpose of the study is to identify the optimal dose level of NP-G2-044 in combination with standard of care (SOC) pegylated liposomal doxorubicin (PLD), and to compare the efficacy and safety of NP-G2-044+PLD vs. PLD alone in participants with platinum-resistant ovarian cancer (PROC).

Key Eligibility Inclusion Criteria:

Participants must have confirmed ovarian high-grade serous carcinoma (histologically or cytologically)



Participants should have platinum resistance

No PLD use after developing platinum resistance

Participants must have had bevacizumab in a prior treatment line or must have been ineligible for bevacizumab therapy.



ECOG status 0-1

Measurable disease per RECIST v1.1 as assessed by local site Investigator/radiologists in the Dose Escalation phase, and assessed by BICR in the Dose Optimization phase and Phase 3; lesions situated in previous irradiated areas are considered measurable if progression has been demonstrated in such lesions

Left ventricular ejection fraction > 50%

Participants with adequate hematologic function based on following



Absolute neutrophil count >/= 1.5 × 109/L

Platelet count >/= 100 × 109/L

Hemoglobin >/= 9.0 g/dL

Albumin >/= 3.0 g/dL



Adequate coagulation parameters based on the following:



Prothrombin time-internationalization normal rate (INR)/partial thromboplastin time < 1.5 × upper limit of normal (ULN)

Partial thromboplastin time or activated partial thromboplastin time < 1.25 × ULN



Participants must have adequate hepatic and renal function. For hepatic function, total bilirubin should be less than 1.5 times the ULN. For renal function, serum creatinine clearance must be at least 45 mL/min.

Participants of childbearing potential (defined as sexually mature women who have not undergone surgical sterilization or been postmenopausal for at least 12 months if over 55 years of age) must have a negative pregnancy test within 72 hours before starting treatment. These participants must use highly effective contraception or abstain from heterosexual activity from screening through 120 days after the last dose of study medication.

Applicable Disease Sites
Ovary

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital