Time spent on Dabrafenib+Trametinib 

Interesting spider graph at ECC2015 on Dabrafenib and Trametinib a known combination of a Braf inhibitor and a Mek inhibitor. A subset of patients can make it longer than others -meaning that their tumour resistance to the treatment is occurring much later (>2 years). As seen patients with a slow reduction of tumours tend to stay longer on treatment than the ones experiencing a rapid shrinkage.

ORR* to

immunotherapy in patients subgroups CheckMate 067

Patients with  PDL1>5% respond well to

both combination Ipi +Nivo or Nivo alone.

Patients wild type respond better to combination Nivo+ IPI than to Nivo alone.


Finally patients with lower LDH have respond the best to both treatments (combi or mono).

Efficacy of treatments for the total number of patients is known from ASCO2015 -median PFS is 11.5 months for NIVO + IPI versus 6.9 months for NIVO alone and 2.9 months for IPI alone.
* - overall response rate

Educative at #ECC2015: Treatments landscape in melanoma 

Treatment options for both Braf positive and Braf wild melanoma.
Obviously there are more choices and opportunities to alternate the treatments for Braf positive patients.
Chemotherapy is the last option. Strict monitoring at 6-8 months looks essential to early catch the disease progression.
https://www.europeancancercongress.org/Scientific-Programme/Abstract-search#
Abstract 3303.

Novartis targeted therapy snippet

Discussion with Novartis about the Dabrafenib/Trametinib combo - as we suspected you dont really need to keep the Trametinib in the fridge - they will be re-issuing advice to corroborate this shortly ...

Next targeted therapy combo Cobimetinib plus Vemurafenib

Combimetinib plus Vemurafenib versus Vemurafenib alone

Copy number of BRAF not relevant for response
13% patients had additional mutations at the beginning BUT it has no effect on response.

and no surprise- combo works better than mono therapy! 

T-Vec plus Pembro phase 1b

Update on Phase 1b study

We've been waiting for this one .

T-Vec alone wasn't convincing in the past but this is the combination with Pembro.


Treatment naive patients, 20% Braf pos

Flat dose 200 mg Pembro Q2W used

Side effects typical for immune therapy

Well-tolerated

Unfortunately NO COMMENT on response rates!!!! 

Next step: will be tested in a Phase 3 trial

Sunday Melanoma Session at ECC2015- Nivo then Ipi versus Ipi then Nivo in Stage 4 Melanoma

Update on CHECKMATE 064- Hodi

Phase 2 , Nivo post Ipi vs Ipi post Nivo in Melanoma

140 patients

Ipi 3 mg
Nivo 3 mg

1 prior therapy allowed but no Immuno.



Disease progression more in Ipi first

More side effects on Nivo first

Immune- related side effects
Similar to direct combo

50 vs 31% Hepatitis Nivo/ Ipi vs Ipi/ Nivo


ORR 41 vs 20 % confirmed ORR 

TUMOUR BURDEN REDUCES FASTER on Nivo first

So- conclusion : Nivo then Ipi higher response rate than Ipi then Nivo but more side effects, similar to what one sees when Ipi and Nivo are giving at the same time.

Caroline Robert commented- surprising as currently one thought that Ipi recruits  T-cells that are then activated by PD1.
Also good as it could allow to start with PD1 and only add Ipi when needed, avoiding to limit side effects

Ipi plus Nivo better Nivo/Ipi better than Ipi/ Nivo

To be tested 
Intra-tumoral injection of Ipi plus Pd1