Pembrolizumab With Ataluren in Patients With Metastatic pMMR and dMMR Colorectal Carcinoma or Metastatic dMMR Endometrial Carcinoma: the ATAPEMBRO Study

ConditionsColorectal Cancer Endometrium Cancer

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age18+

SponsorAcademisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

About this trial

Single Center, open label, Phase I-II trial designed to test the safety and efficacy of the combination of Ataluren and Pembrolizumab for the treatment of metastatic mismatch repair deficient and proficient colorectal adenocarcinoma and metastatic mismatch repair deficient endometrial carcinoma.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Have at least one lesion with measurable disease as defined by 10mm in longest diameter for a soft tissue lesions or 15mm in short axis for a lymph node by RECIST 1.1 and irRC criteria for response assessment.

Have received at least 1 prior cancer therapy regimen for metastatic CRC, or have refused palliative chemotherapy. In the latter case this should have been documented.

Have a life expectancy of greater than 3 months.

Have normal organ and marrow function as defined in protocol

Disqualifiers

None

Trial design

Design model

Sequential

Treatments tested in this trial

Ataluren + Pembrolizumab
Drug
Ataluren and Pembrolizumab combination therapy

Treatment groups

47 Participants

are divided into 3 treatment groups

Group A: Phase I dMMR and pMMRExperimental treatment 1 intervention

Group B: Phase II dMMRExperimental treatment 1 intervention

Group C: Phase II pMMRExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Incidence of treatment-Emergent Adverse Event and the determination of the maximum tolerable dose of Ataluren.

To characterize toxicities and side effects of Ataluren when combined with pembrolizumab in patients with pMMR CRC, dMMR mCRC and dMMR EC. Recorded on Adverse Events form and ranking adverse event severity according to the NCI Common Terminology Criteria for Adverse Events v3.0

Time frame

Initial dose escalation for Ataluren for first 12 pt in groups of 3, which will approximately take 1 year. All adverse events will be further reported at study compeltion: expected to be after 2 years

Objective response rate

Measured by immune-related response criteria

Time frame

30 weeks

Secondary outcomes

Immune-related progression free survival

irPFS

Time frame

21 weeks and 30 weeks

Overall survival

Time frame

trough study completion: expected after 2 years.

Progression free survival

non immune related PFS

Time frame

at 30 weeks

Overall response rate

ORR

Time frame

trough study completion: expected after 2 years.

Other outcomes

Sequencing data comparison before and after treatment

mRNA and DNA sequencing measurements from normal blood, tumor, metastatic and polyp tissue: outcome measure will be mutations in DNA and RNA.

Time frame

trough study completion: expected after 4 years.

Identification of prediction biomarkers

Biomarker measurements from normal blood: CEA and neoantigens (peptides)

Time frame

trough study completion: expected after 4 years.

T-cell activation against neo-antigens

Elispot assays from PBMCs derived from patient blood samples to check for IFN-gamma production after peptide stimulation

Time frame

trough study completion: expected after 4 years.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Lead sponsor

Merck Sharp & Dohme LLC

Collaborator

PTC Therapeutics

Collaborator

Source ClinicalTrials.gov

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