Wednesday, November 13, 2019 IND 221 Publication: Tinker AV, Hirte HW, Provencher DM, Butler MO, Ritter H, Tu D, Azim HA, Paralejas P, Grenier N, Hahn SA, Ramsahai J, Seymour L. Dose-ranging and cohort-expansion study of monalizumab(IPH2201) in advanced gynecologic malignancies: A trial of the Canadian Cancer Trials Group (CCTG):IND221. Clin Cancer Res 25: 6052-60, 2019 https://clincancerres.aacrjournals.org/content/25/20/6052.long The purpose of this study was to test the safety of a new drug, IPH2201, to see what effects it has on this type of cancer. Results: A total of 58 participants were evaluable. The RP2D was 10 mg/kg i.v. every 2 weeks. Dose proportionality and 100% NKG2A saturation were observed. Related adverse events were mild: headache, abdominal pain, fatigue, nausea, and vomiting. Grade 3 related adverse events were nausea (1), vomiting (1), dehydration (1), fatigue (2), anorexia (1), dyspnea (1), and proctitis (1). Dose-limiting toxicities were not observed. Hematologic and biochemical changes were mild and not dose related. Best response was SD: part 1, 7 of 18 (39%) [3.4 months (1.4–5.5)], and part 2, 7 of 39 (18%) [1.7 months (CX) to 14.8 months (END)]. Neither a predictive biomarker for SD nor evidence of pharmacodynamic effects was identified. There was a trend to significance between a reduction in lymphocyte HLA-E total score and pharmacodynamics. Conclusions: Monalizumab 10 mg/kg i.v. every 2 week is well tolerated in patients with pretreated gynecologic cancers. Short-term disease stabilization was observed. Future studies should assess combinations with other agents, including immunotherapeutics. IND 208 Publication: Goodwin R, Jonker D, Chen E, Kennecke H, Cabanero M, Tsao MS, Vickers M, Bohemier C, Lim H, Ritter H, Tu D, Seymour L. A phase Ib study of a PI3Kinase inhibitor BKM120 in combination with panitumumab in patients with KRAS wild-type advanced colorectal cancer (ONLINE). Invest New Drugs 2019. https://link.springer.com/article/10.1007%2Fs10637-019-00814-3 Background: Resistance to Epidermal Growth Factor inhibition (EGFRi) in patients with KRAS wild-type (wt) Colorectal Cancer (CRC) may occur as a result of PI3K/AKT/mTOR signaling. We conducted a study to establish the recommended phase II dose (RP2D) and response rate of panitumumab, an EGFRi, plus BKM120, a PI3K inhibitor, in advanced CRC. Methods Patients with chemotherapy refractory KRAS wt CRC, who were EGFRi naive were enrolled. A 3 + 3 dose escalation design was utilized. The starting dose of panitumumab was 6 mg/kg iv every 2 weeks with BKM120 at 60 mg oral daily. Results Nineteen patients were treated and 17 were evaluable for response. The starting dose was not tolerable (mucositis, fatigue). At dose level (DL) 1, three of six patients discontinued treatment due to toxicity, DL − 1 had no significant toxicity. Panitumumab 6 mg/kg iv q 2 weeks with BKM120 60 mg given 5 out of 7 days per week was declared the RP2D. One patient (5.9%) who was PTEN and PIK3CA negative by IHC had a partial response, seven had stable disease, and nine had disease progression. Conclusion: Panitumumab (6 mg/kg iv q 2 weeks) with BKM120 60 mg given 5 out of 7 days per week was declared the RP2D. Toxicities including fatigue, rash and mucositis. There was little evidence of activity in this biomarker unselected cohort.
