Here’s a link to a press item describing a RCT to compare the safety of R-CHOP plus tafasitamab (MOR208) to R-CHOP plus tafasitamab and lenalidomide (Revlimid) in treatment-naive DLBCL
Treatment -naive DLBCL is cured ~60% of the time with backbone R-CHOP in previously untreated patients with this aggressive lymphoma - which is less likely to be cured second line.
Red flag: This is a safety study in a first line treatment setting.
Is it ethical to compare 2 experimental approaches in a curative setting? 1 or both study combinations may lead to unanticipated AEs leading to decreased efficacy relative to SOC: R-CHOP.
the study teams may need to expose more patients to experimental treatments over a longer period of time to know which should to bring forward in an RCT against R-CHOP (compared to studying each combination against R-CHOP from the start.)
I feel this should be the way forward - do 2 studies up front:
R-CHOP plus tafasitamab VS R-CHOP (half get SOC)
R-CHOP plus tafasitamab and lenalidomide VS R-CHOP (half get SOC)
The above comparisons provide a reference point in each study for judging safety and signals for efficacy relative to the SOC. As done, both may be less, or as, safe as R-CHOP and we would not know.
Endpoints copied from study enrolling 60 patients: https://clinicaltrials.gov/ct2/show/NCT04134936
Primary Outcome Measures :
- Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: 6 months approximately ]
Secondary Outcome Measures :
Objective Response Rate (ORR) at the end of treatment [ Time Frame: 6 months approximately ]
Metabolic, PET-negative complete response (CR) rate at the end of treatment [ Time Frame: 6 months approximately ]
Incidence and severity of adverse events (AEs) in the follow-up period [ Time Frame: 18 months approximately ]
Best Objective Response Rate (ORR) until the end of study [ Time Frame: 24 months approximately ]
Metabolic, PET-negative complete response (CR) rate until the end of study [ Time Frame: 24 months approximately ]
Progression-free survival (PFS) at 12 and 24 months [ Time Frame: 24 months approximately ]
Event-free survival (EFS) at 12 and 24 months [ Time Frame: 24 months approximately ]
Time to next anti-lymphoma treatment (TTNT) [ Time Frame: 24 months approximately ]
Overall survival at 12 and 24 months [ Time Frame: 24 months approximately ]
Anti-tafasitamab antibodies formation [ Time Frame: 12 months approximately ]
Jan 21 addition:
In this safety study there is no titration of the study drugs or dose level groups, 1 or both study drugs are given concurrently with the SOC at the active dose level (determine in other studies).
About me: Karl Schwartz, formerly: patient representative to FDA, president of PAL, CIRB member, NCI Steering Cmt, Vail Methods Workshop faculty. www.lymphomation.org