TiNivo-2 vs CONTACT-03: Trial Design and Key Differences

The first part of a roundtable discussion with Dr. Katie Beckermann, Dr. Monty Pal, Dr. Hans Hammers, Dr. Toni Choueiri, and Dr. Pedro Barata examines the design, findings, and clinical implications of the TiNivo-2 study, with a comparison to CONTACT-03. The discussion addresses key topics, including trial eligibility criteria, the role of immune checkpoint inhibitors and TKIs, and the impact of these strategies on renal cell carcinoma treatment.

Watch part two of this roundtable: TiNivo-2 Efficacy: Breaking Down the Data on TKI and Immunotherapy in RCC Treatment

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Dr. Beckermann:
I’d like to welcome the audience to this GU Oncology Now Roundtable discussion, where we’re really going to get into the data regarding the TiNivo-2 study. And super-excited to be here this afternoon. Topping off my week, really, with amazing colleagues. And just to go around the virtual room, if you will, and I’ll have everyone introduce themselves. I haven’t introduced myself. I’m Katie Beckermann, I’m an assistant professor focused in GU Oncology at Vanderbilt University.

And Dr. Pal, I have you next on my screen, so I’ll have you go next.

Dr. Pal:
Awesome. Hey, Monty Pal. I’m a GU medical oncologist at City of Hope in Los Angeles.

Dr. Beckermann:
Excited to have you here. And Dr. Hammers, I have you next on my screen.

Dr. Hammers:
Hans Hammers, medical oncologist in UT Southwestern, Dallas, Texas.

Dr. Beckermann:
Great. And Dr. Choueiri, have you next.

Dr. Choueiri:
I’m a medical oncologist from Boston, the city of sports champions.

Dr. Beckermann:
Love it. And Dr. Barata, have you last.

Dr. Barata:
Hey there, I’m a GU oncologist as well. University Hospital Seidman Cancer Center, Case Western, here in Cleveland, Ohio.

Dr. Beckermann:
Well, thank you all so much for coming this afternoon. And maybe just to start, it might be helpful for the audience if somebody is not as up-to-date as we all are on the data. Dr. Pal, I might have you give us the background. You were so integral, you and Dr. Choueiri in CONTACT-03. And why did we need this TiNivo-2 study?

Dr. Pal:
Yeah, yeah. I mean, I think that Toni and I had talked about the design of CONTACT-03 for years ahead of the study starting. And it was really built on the premise that when we were receiving second opinions and consultations from the community, we would see this very pervasive practice of people administering frontline checkpoint inhibitors, and carrying it on the second-line setting and the third-line setting. Very much like trastuzumab for breast cancer, or the HER2-directed therapy just stays on board in perpetuity.

And of course, I think that that comes at a significant financial cost. There’s the toxicity-based costs associated with that. So we really conceived of CONTACT-03, and it was a really clean design, A versus A plus B here, with A being cabozantinib, B being atezolizumab. And I think that that really, as a negative study, did initially put the nail in the coffin of using sequential checkpoint inhibitors.

But I think TiNivo-2, which Toni led, really played a very, very key role, in the sense that it provided further evidence for those that said, “Well, CONTACT-03 used a PD-L1 inhibitor. We want to see some evidence based on the context of PD-1.”

Dr. Beckermann:
That’s great. And Dr. Choueiri, maybe when you were in those initial discussions then, thinking about TiNivo-2 and testing the idea of maybe it was just PD-L1 that was the lack of benefit in CONTACT-03. Can you tell us a little bit about the design of TiNivo-2?

Dr. Choueiri:
Yeah, TiNivo-2 is a randomized Phase 3 trial where patient who experienced disease progression on prior PD-1 PD-L1 inhibitor end up mostly PD-1 inhibitor. They could not have received the prior TKI, meaning we had almost 30% of patient that ending up that just got immunotherapy only and went on TiNivo-2. Those patients were randomized to receive full-dose tivozanib at the FDA-approved dose, 1.34 milligram, three week on, one week off, or the combination with nivolumab but at a lower dose of tivozanib, .89. And the reason was the incidence of hypertension that happened with the combination on the first part of the study, and then on the Phase 1 part of the study. Despite that this was, I would say, easily managed, but this was at the heart of Project Optimus and other attempts from the FDA to get the right dose.

And one differential here, in term of eligibility criteria with CONTACT-03, actually two. One was this study was only clear cell, where CONTACT-03 was mostly clear cell, but it had some non-clear cell. And I think a large part of the design was Dr. Pal and his affinity for non-clear cell. So we allowed papillary and others.

And the second differential with TiNivo-2, which I think ends up answering in part an important question, is that the last therapy does not need to have been an immune checkpoint inhibitor. And we end up with 30% of patient or a bit less where the last therapy was a TKI in general before being randomized.

Dr. Beckermann:
That’s helpful, highlighting those differences that we see between the trial designs of CONTACT-03 and TiNivo-2.