Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

Hello,

If we are combining a novel small molecule with pembro, do we want to measure pembro PK as well as our own drug in the Phase 1 trial? To me this sounds insane, as pembro is an immutable fixed dose, there is no reason for a small molecule effect on its PK, there are close to 100 novel drug+pembro combos in clinic.

And I am assuming because this is for a cancer indication, preclinical drug-drug interaction studies are not mandatory?

I would think not - I agree with your rationale.

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Glen Park PharmD
Executive Director, Regulatory Affairs and Quality Assurance
Jersey City NJ
United States
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Original Message:
Sent: 18-May-2020 09:53
From: Anonymous Member
Subject: oncology phase 1 combination treatment

This message was posted by a user wishing to remain anonymous

Hello,

If we are combining a novel small molecule with pembro, do we want to measure pembro PK as well as our own drug in the Phase 1 trial? To me this sounds insane, as pembro is an immutable fixed dose, there is no reason for a small molecule effect on its PK, there are close to 100 novel drug+pembro combos in clinic.

And I am assuming because this is for a cancer indication, preclinical drug-drug interaction studies are not mandatory?

Is your novel drug already dosed in humans? i.e. FIH study? Or you are just proposing to do FIH study with Pembro?

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GRSAOnline
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Original Message:
Sent: 18-May-2020 09:53
From: Anonymous Member
Subject: oncology phase 1 combination treatment

This message was posted by a user wishing to remain anonymous

Hello,

If we are combining a novel small molecule with pembro, do we want to measure pembro PK as well as our own drug in the Phase 1 trial? To me this sounds insane, as pembro is an immutable fixed dose, there is no reason for a small molecule effect on its PK, there are close to 100 novel drug+pembro combos in clinic.

And I am assuming because this is for a cancer indication, preclinical drug-drug interaction studies are not mandatory?

This message was posted by a user wishing to remain anonymous

The novel drug is not dosed in humans and therefore this is an FIH with Pembro. 

In all of the posts on ct.gov, no combo treatment with pembro is evaluating pembro PK alone when in combination. The only evaluation listed as a secondary endpoint in most cases is PK of pembro+small molecule in combination; PK of small molecule when in combination (but no PK of pembro when in combination). 

Is there any relevant regulatory guidance which states that pembro PK in combination should be assessed?
Original Message:
Sent: 19-May-2020 12:42
From: Narayan Rao
Subject: oncology phase 1 combination treatment

Is your novel drug already dosed in humans? i.e. FIH study? Or you are just proposing to do FIH study with Pembro?

------------------------------
GRSAOnline

Original Message:
Sent: 18-May-2020 09:53
From: Anonymous Member
Subject: oncology phase 1 combination treatment

This message was posted by a user wishing to remain anonymous

Hello,

If we are combining a novel small molecule with pembro, do we want to measure pembro PK as well as our own drug in the Phase 1 trial? To me this sounds insane, as pembro is an immutable fixed dose, there is no reason for a small molecule effect on its PK, there are close to 100 novel drug+pembro combos in clinic.

And I am assuming because this is for a cancer indication, preclinical drug-drug interaction studies are not mandatory?

This message was posted by a user wishing to remain anonymous

data collection (pk, pd, safety, etc...) especially if the novel drug is used in combination with an approved mab, is not necessarily should be looked as regulatory check boxes but rather is very important for characterization of the combination in patients  to build a baseline critical parameters so that the advanced drug development of the combo in the target patient population can be rationally constructed to reach the pivotal trial stage. I would strongly recommend to consult your pharmacologist/clinician before deciding anything. It is very difficult to provide any feedback with limited information you are providing. I would not conclude based on looking at brief details on the ct.gov unless you get to see the full protocol.
Original Message:
Sent: 19-May-2020 12:59
From: Anonymous Member
Subject: oncology phase 1 combination treatment

This message was posted by a user wishing to remain anonymous

The novel drug is not dosed in humans and therefore this is an FIH with Pembro.

In all of the posts on ct.gov, no combo treatment with pembro is evaluating pembro PK alone when in combination. The only evaluation listed as a secondary endpoint in most cases is PK of pembro+small molecule in combination; PK of small molecule when in combination (but no PK of pembro when in combination).

Is there any relevant regulatory guidance which states that pembro PK in combination should be assessed?
Original Message:
Sent: 19-May-2020 12:42
From: Narayan Rao
Subject: oncology phase 1 combination treatment

Is your novel drug already dosed in humans? i.e. FIH study? Or you are just proposing to do FIH study with Pembro?

------------------------------
GRSAOnline

Original Message:
Sent: 18-May-2020 09:53
From: Anonymous Member
Subject: oncology phase 1 combination treatment

This message was posted by a user wishing to remain anonymous

Hello,

If we are combining a novel small molecule with pembro, do we want to measure pembro PK as well as our own drug in the Phase 1 trial? To me this sounds insane, as pembro is an immutable fixed dose, there is no reason for a small molecule effect on its PK, there are close to 100 novel drug+pembro combos in clinic.

And I am assuming because this is for a cancer indication, preclinical drug-drug interaction studies are not mandatory?

The combination does not have a clear PK.  Each individual have PK which is sufficient however, the combo in question needs to be checked prior to phase 1. 

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Bani Tchekanova
Escondido CA
United States
------------------------------

Original Message:
Sent: 18-May-2020 09:53
From: Anonymous Member
Subject: oncology phase 1 combination treatment

This message was posted by a user wishing to remain anonymous

Hello,

If we are combining a novel small molecule with pembro, do we want to measure pembro PK as well as our own drug in the Phase 1 trial? To me this sounds insane, as pembro is an immutable fixed dose, there is no reason for a small molecule effect on its PK, there are close to 100 novel drug+pembro combos in clinic.

And I am assuming because this is for a cancer indication, preclinical drug-drug interaction studies are not mandatory?

Hello Beni,

I don't think you need Pembrolizumab PK data in your case but only PK data for your drug. However, you need to monitor safety of the combination of both drugs. 

Good luck with your study.

Olga

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Olga Peycheva
Regulatory and Study Start Up Specialist (Clinical trials)
Solutions OP Ltd
https://solutionsop.co.uk/
United Kingdom
------------------------------

Original Message:
Sent: 18-May-2020 09:53
From: Anonymous Member
Subject: oncology phase 1 combination treatment

This message was posted by a user wishing to remain anonymous

Hello,

If we are combining a novel small molecule with pembro, do we want to measure pembro PK as well as our own drug in the Phase 1 trial? To me this sounds insane, as pembro is an immutable fixed dose, there is no reason for a small molecule effect on its PK, there are close to 100 novel drug+pembro combos in clinic.

And I am assuming because this is for a cancer indication, preclinical drug-drug interaction studies are not mandatory?

This message was posted by a user wishing to remain anonymous

Disagree, if its a novel drug in combo with Pembro, it would be prudent to see if pk of Pembro is impacted with the novel drug!

I agree with the Anon "data collection (pk, pd, safety, etc...) especially if the novel drug is used in combination with an approved mab, is not necessarily should be looked as regulatory check boxes but rather is very important for characterization of the combination in patients  to build a baseline critical parameters so that the advanced drug development of the combo in the target patient population can be rationally constructed to reach the pivotal trial stage.'"

Original Message:
Sent: 22-Nov-2023 05:30
From: Olga Peycheva
Subject: oncology phase 1 combination treatment

Hello Beni,

I don't think you need Pembrolizumab PK data in your case but only PK data for your drug. However, you need to monitor safety of the combination of both drugs. 

Good luck with your study.

Olga

------------------------------
Olga Peycheva
Regulatory and Study Start Up Specialist (Clinical trials)
Solutions OP Ltd
https://solutionsop.co.uk/
United Kingdom

Original Message:
Sent: 18-May-2020 09:53
From: Anonymous Member
Subject: oncology phase 1 combination treatment

This message was posted by a user wishing to remain anonymous

Hello,

If we are combining a novel small molecule with pembro, do we want to measure pembro PK as well as our own drug in the Phase 1 trial? To me this sounds insane, as pembro is an immutable fixed dose, there is no reason for a small molecule effect on its PK, there are close to 100 novel drug+pembro combos in clinic.

And I am assuming because this is for a cancer indication, preclinical drug-drug interaction studies are not mandatory?