RE:RE:Immunogen IncThe Phase 1/2 results of ONCYs GOBLET Cohort 4 that enrolled patients with advanced/metastatic unresectable SCCA (anal cancer) who failed prior systemic therapy appear to be better than ImmunoGens results obtained from both of ImmunoGens Phase 2 SORAYA study to support accelerated approval by the FDA, and its followup Phase 3 MIRASOL study to support confirmation of the accelerated approval.
MIRASOL demonstrated an ORR of 32% and mDOR 6.9 months as seen in the single arm Phase 2 SORAYA study that resulted in the accelerated approval by the FDA. The Phase 3 MIRASOL study to support confirmation of the accelerated approval enrolled 550 patients with 5 complete responses (<1% CRs) reported.
Of the 8 SCCA patients in ONCYs GOBLET Cohort 4 (pelareorep+atezolizumab+/-chemotherapy) in advanced/metastatic unresectable SCCA, one achieved a complete response (ongoing at 12 months) (>12% CRs) and 2 patients have achieved partial responses (25% PRs) (one at week 8 and one ongoing at week 16). Five patients had a best response of progressive disease. The interim ORR is 37.5%. Final ORR, median PFS, and median OS are pending.
In a seperate study involving a CPI a phase II single-arm (NCT02314169) was conducted, involving 37 patients with SCCA, irrespective of PD-L1 expression, received nivolumab as second line or subsequent treatment. An ORR of 24% was reported, with 2 complete responses (5.4% CRs) and 7 partial responses (19% PRs). Median PFS (mPFS) and mOS were 4.1 and 11.5 months respectively.
In Mercks Phase Ib KEYNOTE-028 (NCT02054806) - a multicenter, multicohort, single-arm trial that evaluated pembrolizumab monotherapy in patients with 20 different PD-L1-positive tumor types, the cohort of patients with advanced heavily pretreated anal cancer, among the 24 patients with squamous histology, resulted in 4 obtaining a confirmed PR, for an ORR equal to 17%. Median PFS and OS were 3.0 and 9.3 months, respectively, similar to those reported with nivolumab, while median duration of response (DOR) was not reached at the time of analysis.
In the CARACAS study, an open-label, multicenter, randomized, phase II trial (NCT03944252), 60 patients diagnosed with metastatic SCCA progressing after one or more lines of treatment were randomized (1:1 ratio) to receive avelumab alone (arm A) or combined with cetuximab (arm B) [45]. 4 patients were HIV-positive. Primary endpoint was ORR, and at least 4 responses out of 27 patients per arm had to be observed to declare the study positive. The primary endpoint was met in arm B, with an ORR of 10% in arm A and 17% in arm B. As to the secondary endpoints, mPFS was 2.0 months and 3.9 months, while mOS was 13.9 months and 7.8 months in arm A and B respectively. This latter result should be interpreted cautiously due to the non-comparative design of the trial, the the small size of the sample and the potential confounding effects of some unbalanced prognostic factors.
In the phase II basket-trial NCT03074513 which evaluated the combination of the anti PD-L1 atezolizumab plus bevacizumab in patients with previously treated, immunotherapy-nave, HPV-associated solid tumors. Results for SCCA patients were presented at ESMO 2021: 20 patients with unresectable SCCA were enrolled. ORR was 10% (2 PRs). mPFS and mOS were 4.1 months and 11.6 months respectively
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