Background: Intravenous (IV) docetaxel and oral prednisone is a standard of care regimen in patients (pts) with mCRPC. ModraDoc006 is an oral formulation of docetaxel. To enhance bioavailability of ModraDoc006, it is co-administered with ritonavir (/r). The ModraDoc006 and ritonavir combination is active in multiple docetaxel and cabazitaxel-resistant prostate cancer cell-lines The oral combination (ModraDoc006/r) was compared to IV docetaxel in a randomized phase 2b study in pts with mCRPC evaluating two doses of ModraDoc006/r (30-20/200-100 mg and 20-20/200-100 mg). Data on outcomes in the larger cohort, receiving the lower dose, are being presented. Methods: Eligible pts had mCRPC, performance status of 0-1 and no prior chemotherapy for mCRPC. Sixty-two pts were enrolled in open label 1:1 randomized study comparing ModraDoc006/r 20-20 mg combined with 200-100 mg ritonavir in a bi-daily weekly schedule (“20-20/200-100 mg”), with IV docetaxel 75 mg/m² in 21-day cycles. All pts received 5 mg oral prednisone twice daily. Primary endpoint was radiographic progression free survival (rPFS) per PCWG-3 criteria. Secondary objectives included ORR, PSA-PFS, time to skeletal related events, disease control rate, duration of response, and safety assessments. Results: 31 pts were enrolled on IV docetaxel 75 mg/m² and 31 on ModraDoc006/r 20-20/200-100 mg. Of these, 57 were included in the analysis for rPFS, and 32 pts with measurable disease were included in the ORR analysis. Median PSA was 46 (range 1 to 1460 ng/ml). Prior therapy with enzalutamide in 8 pts, abiraterone in 10 pts. ModraDoc006/r was better tolerated with 0% all grades neutropenia and anemia, as compared to 26% (19% ≥G3) and 16% respectively on IV docetaxel. Neuropathy was significantly reduced at 9.7% G1 only on ModraDoc006/r vs 9.7% G1 and 19.4% G2 on IV docetaxel, whereas alopecia was reduced to 16.1% G1 and 6.5% G2 on ModraDoc006/r vs. 22.6% G1 and 19.4% G2 on IV docetaxel. GI toxicities were broadly comparable with diarrhea 32% (3% ≥G3) vs 29%, nausea 29% vs 13% and stomatitis 3% (G3) vs 13% (3% ≥G3), respectively. Conclusions: ModraDoc006/r demonstrated a favorable safety profile and comparable efficacy to IV docetaxel in pts with mCRPC, thus providing a compelling rationale for conduct of an expanded pivotal program. A key clinical program focus is the comparison of ModraDoc006/r to best available therapy in refractory mCRPC. Studies of ModraDoc006/r in other malignancies are also in active development. Clinical trial information: NCT04028388.