Welcome back to Season 4! This episode of Novel Targets was recorded at the 2018 annual meeting of the American Association for Cancer Research (AACR) in Chicago. This time around, we’re talking about cancer immunotherapy clinical practice, pitfalls in trial design/interpretation, emerging biomarkers, and possibilities for future cures in some patients.

Professor Tom Powles

Tom Powles (Barts Cancer Centre) is a regular on the podcast. He previously featured in Episode 7 , where he talked about some of his experience with the checkpoint inhibitor, atezolizumab, in bladder cancer.

In the latest show, he guides us through his thinking about cancer immunotherapy clinical trials, and some of the practical issues that arise, and some important pitfalls to watch out for. He highlights the challenges with chemotherapy control arms as well as some key hazards to consider that are associated with cross trial comparisons.

Professor Powles is one of the few medical oncologists we know who can eloquently discuss cancer immunotherapy across tumour types.

A transcript of the full interview is available on Biotech Strategy Blog (sub req’d). See post: Stacking up evidence from IO clinical trials.

 

Dr Roy Herbst

We last spoke with Dr Herbst (Yale Cancer Center) at the 2014 Society for Immunotherapy of Cancer meeting (SITC). He featured in one of the prologues prior to the launch of the podcast. We’ve come a long way in cancer immunotherapy since then!

Dr Herbst (@DrRoyHerbstYale) was the discussant for the phase 3 KEYNOTE-189 trial data presented at the AACR meeting. Described as “practice changing” in lung cancer, the results have been published in The New England Journal of Medicine.

In this episode, we also hear what his vision for the future of cancer immunotherapy in lung cancer is.

Dr Hossein Borghaei

Dr Borghaei (Fox Chase Cancer Center) offers his commentary on some of the lung cancer data presented at the 2018 AACR annual meeting.

To the surprise of many, data for three phase 3 cancer immunotherapy trials (KEYNOTE- 189, CheckMate 227 and IMpower150) in non-small cell lung cancer were presented at the meeting.

Dr Borghaei (@HosseinBorghaei) was one of authors on The New England Journal of Medicine paper for the CheckMate 227 trial of ipilimumab and nivolumab in patients with high tumour mutational burden (TMB).

Dr Jack West

Dr West (Swedish Cancer Institute) focuses on lung cancer in his Seattle practice and generously gives of his time to ensure high quality patient education through his leadership of GRACE (Global Resource for Advancing Cancer Education).

He last featured on the podcast in episode 3 from ASCO 2015.

In this episode, Dr West (@JackWestMD) offered a clinical perspective on some of the lung cancer data presented at AACR, and whether the data would influence his clinical practice.

We’ve collated the opinions expressed by Drs Herbst, Borghaei West and Sandler on Biotech Strategy Blog (sub req’d). See post: The PD-1 Gorilla is Back!

 

Dr Alan Sandler

Alan Sandler is the Global Head of the lung cancer franchise at Roche Genentech. After a distinguished career as an academic lung cancer physician, he’s now working in industry.

In this episode, Dr Sandler highlights results from the IMpower150 trial that was presented at AACR, which for the first time show significant efficacy of a checkpoint inhibitor combination in patients with an EGFR mutation and ALK aberration for whom prior TKI therapy stopped working.

Disclaimer: Although Genentech sponsored this episode of the podcast, the company had no input into the questions we asked or any editorial control over what we included on the podcast.

The results from the IMpower150 trial have since been published in The New England Journal of Medicine (link).

Professor Charles Swanton FRS

Charlie Swanton (UCL & Francis Crick) is at the forefront of the convergence of cancer immunotherapy and genomics.

Professor Swanton (@CharlesSwanton) was an invited speaker in the plenary session at AACR 2018, where he discussed some of the latest data from the TRACERx studies in lung and renal cancer.

In this episode, we hear about why the type of mutations (trunk versus branch) patients have may matter if you want to avoid resistance to treatment and generate long term remissions.

The research he is leading has the potential to revolutionize treatment. If you’d like to catch up some of his seminal findings in renal cancer – and there are a lot more to come – then here are some of the recent key papers published to date:

  • Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal (link)
  • Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal (link)
  • Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal (link)
  • Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing (link)

A transcript of the full interview with Professor Swanton is available on Biotech Strategy Blog (sub req’d). See post: How Charles Swanton plans to revolutionize treatment of Lung and Renal cancers.

Since the podcast interview was recorded, Professor Swanton, has been elected a Fellow of the Royal Society (FRS). Congratulations to him and the other scientists who received this prestigious recognition of their research.

 

Dr Nicky McGranahan

One of the scientists working with Prof Swanton on the TRACERx project is Nicky McGranahan. He’s now a Group Leader at the CRUK Lung Cancer Center of Excellence at UCL.

Dr McGranahan (@NickyMcGranahan) takes us through some of the scientific challenges associated with measuring Tumour Mutation Burden (TMB).

On this episode we didn’t have time to discuss some of his pioneering work on loss of heterozygosity (LOH) and the implications of this for neoantigen selection.

We spoke with Prof Swanton about this for Biotech Strategy Blog subscribers back at the 2017 AACR-EORTCI-NCI Cancer Therapeutics and Molecular Targets meeting where the data was presented by Rachel Rosenthal, pictured at her #Targets17 poster.

Here’s a link to their TRACERx lung publication in CellAllele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution.

 

Dr David Fabrizio

Dr Fabrizio works at Foundation Medicine. Their FoundationOne test was used for the measurement of Tumour Mutational Burden (TMB) in the CheckMate 227 trial.

In this episode, he talks about TMB as an emerging biomarker in cancer immunotherapy, something we can expect to hear more of at future meetings. Dr Fabrizio is pictured at the #AACR18 poster he presented.

Additional perspectives from Drs Fabrizio and McGranahan on TMB as a biomarker is available on Biotech Strategy Blog (sub req’d). See post: Can TMB help select patients for lung cancer therapy or not?

 

Dr Kunle Odunsi

Dr Odunsi (Roswell Park) gave a “Meet the Expert” talk at AACR where he talked about strategies to reprogram the tumour microenvironment.

Biotech Strategy Blog subscribers can read more about the innovative, pioneering work being down at Roswell park into targeting TGF β. See post: Targeting TGF β and the tumour microenvironment.

In this episode, Dr Odunsi (@KunleOdunsiMD) offers his strategic perspective on the limitations of biomarkers such as TMB, and how it is likely going to take analyzing “Big Data” in order to personalize cancer immunotherapy.

 

Dr Lizzie Coker

Lizzie Coker (@LizzieCoker) responded to our pre #AACR18 “Cancer New Voices” social media campaign, so we went round to her poster at AACR for a chat.

She’s a computational biologist at the Sanger Institute in Cambridge and you’ll hear her describe the post-doctoral work she did at the Institute of Cancer Research in London.

There’s also a great story about how she was able to use social media to great effect in her career as a young scientist.

Here’s a link to access the public canSAR dataset (‪@canSAR_ICR‬) she mentions.

Sponsorship

This episode was sponsored by Genentech. We’re grateful to their ongoing support of the podcast. What we do is editorially independent and sponsors have no control over the topics we cover, who we interview, or the questions we ask.

 

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