90Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies

AbstractBackgroundFor patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering 90Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine.MethodsFifty-eight patients with three (2–7) median prior treatments were treated on Arm A (N=29, 90Y-clivatuzumab tetraxetan, weekly 6.5mCi/m2doses×3, plus gemcitabine, weekly 200mg/m2 doses×4 starting 1week earlier) or Arm B (N=29, 90Y-clivatuzumab tetraxetan alone, weekly 6.5mCi/m2doses×3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated.ResultsCytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ⩾1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3–9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan–Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29–0.86; P=0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1year.ConclusionsClinical studies of 90Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting

Response-specific effects in a joint action task: social inhibition of return effects do not emerge when observed and executed actions are different

Although the inhibition of return (IOR) effect is primarily studied when people act individually, IOR is also observed in social environments where a person observes a partner?s response before executing their own response (social or sIOR). Specifically, an observer takes longer to initiate a response to a target at a location that another individual has just responded to than to another location. The present study was conducted to determine if sIOR emerges when two individuals execute different actions?one participant executed keypress responses and the other completed aiming movements to the same set of stimuli. The two conditions in the present experiment were designed to separate the effects of observing a co-actor?s target information from observing their subsequent response. In the Full Vision condition, observers saw both the target stimuli and the response of the partner. In the Partial Vision condition, observers witnessed the response of the partner, but did not see the target stimulus or any other potentially attention capturing event at the target location. It was found that, although sIOR emerged in the Full Vision condition, sIOR did not emerge in the Partial Vision condition. These and other previous findings on the impact of action goal on sIOR are discussed with reference to the potential contributions of attention and action co-representation mechanisms to the sIOR effect