| Eligibility |
Inclusion Criteria:
1. Male or female = 18 years
2. Histologically or cytologically confirmed diagnosis of any solid tumour
3. Participants with advanced solid tumours who have progressed on standard of care
therapy or for whom no standard therapy is available
4. Participants with advanced pancreatic cancer may also be eligible if they are
considered by the treating physician to be unsuitable or have chosen not to take
chemotherapy treatment.
5. Participants with high grade serous ovarian, fallopian tube and peritoneal ovarian
cancer should have been previously treated with a poly adenosine diphosphate ribose
polymerase (PARP)inhibitor and should have received no more than 3 prior lines of
systemic therapy.
6. Participants who are naïve to a prior treatment with an immune checkpoint inhibitor.
Participants with lung cancer, renal cancer, mesothelioma or melanoma who have
received prior PD-1/PD-L1 or a CTLA4 inhibitor containing treatment will be eligible
if they have experienced objective response to this treatment (as defined by Response
Evaluation Criteria in Solid Tumours [RECIST] 1.1) as part of their most recent
treatment line and have had progressive disease occurring within 6 months of the last
dose of their checkpoint inhibitor containing treatment.
7. Eastern Cooperative Oncology Group (ECOG)Performance Score0 or 1
8. Life expectancy greater than 3 months at the time of recruitment
9. Measurable disease as per RECIST 1.1 (Response Assessment in Neuro-Oncology [RANO]for
glioblastoma multiforme [GBM]) as assessed by the investigator. Lesions situated in a
previously irradiated area are considered measurable if progression hasbeen
demonstrated in such lesions.
10. In Part 1b of the study, at least one lesion suitable for biopsy (with the exception
of brain tumours). If participants have only 1 measurable lesion per RECIST 1.1, the
biopsy specimen should be obtained from a non-target lesion.
11. Haematology and clotting profile at screening with no clinically significant findings:
- Platelet count > 70 x 109/L
- Absolute neutrophil count = 1.5 x 109/dl
-= 9.0 Serum albumin = 26 g/Lg/dL
- International Normalised Ratio (INR) < 1.5
12. Adequate renal and hepatic function:
- Serum albumin = 26 g/L
- ALT and AST = 2.5x ULN (=5 × ULN forparticipants with liver metastases and
biliary tract cancer)
- Bilirubin = 1.5 x ULN
- INR= 1.5 x ULN
- Serum creatinine = 1.5 x ULN
- Calculated creatinine clearance = 40 mL/min (Cockcroft & Gault). Glomerular
filtration rate (GFR) can be used instead of creatinine clearance.
13. Negative blood pregnancy test for women of childbearing potential following a
menstrual period (within 10 days prior to first drug administration)
14. For female participants of child-bearing potential, a willingness to use highly
effective* contraceptive measures adequate to prevent a new pregnancy for the duration
of the study, for at least 6 months after the last dose of MTL-CEBPA or 6 months after
the last dose of pembrolizumab, whichever is longer. For women with reproductive
potential who use a hormonal method of contraception, concurrent use of a second
(barrier) method is recommended.
*Highly effective methods of birth control are defined as those that result in a low
failure rate (i.e., less than 1% per year) when used consistently and correctly (e.g.,
implants, injectables, oral contraceptives, some intrauterine devices, bilateral tubal
occlusion, true sexual abstinence in line with the preferred and usual lifestyle of
the participant, or vasectomised partner). For EU countries in particular, see
additional requirements in:
https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/
2014_09_HMA_CTFG_Contraception.pdf Male participants with partners of child-bearing
potential are required to use barrier contraception plus an additional contraceptive
method that together result in a failure rate of <1% per year during the treatment
period and for at least 3 months after the last dose of MTL-CEBPA or 4 months after
the last dose of pembrolizumab, whichever is longer. Male participants will also be
advised to abstain from sexual intercourse with pregnant or lactating women, or to use
condoms. Abstinence is only acceptable if it is in line with the preferred and usual
lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, post-ovulation methods), declaration of abstinence for the duration of
exposure to investigational medicinal product (IMP), and withdrawal are not acceptable
methods of contraception.
•Note: a woman is considered of child-bearing potential following menarche and until
becoming post-menopausal unless permanently sterile. Permanent methods of
sterilisation include hysterectomy, bilateral salpingectomy and bilateral
oophorectomy. A post-menopausal state is defined as no menses for 12 months without an
alternative medical cause(For EU countries in particular please refer to:
www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_
HMA_CTFG_Contraception.pdf)
15. Able to comply with all the requirements of the protocol.
Exclusion Criteria:
1. Participants who received any prior systemic anticancer therapy investigational
drug(s)including vaccines,within the last 30 days prior to study treatment initiation
(Cycle1 Day 1)
2. Grade > 1 prior treatment-related toxicity at the time of screening, with the
exception of alopecia or Grade 2 neuropathy which may be eligible if recovered
tobaseline and upon discussion with the Sponsor.
3. Participants received prior radiotherapy within 2 weeks of start of study treatment
4. Participants not recovered adequately from major surgery or radiotherapy.
5. Participants with history of clinically significant haemorrhage or gastrointestinal
perforation•Participants with history of bilateral portal vein occlusion
6. Known infection with human immunodeficiency virus (HIV)withCD4+ T-cell counts <350
cells/µL or with a history of acquired immune deficiency syndrome (AIDS)-defining
opportunistic infection
7. Participants with known history of infection with hepatitis B(HBV)(defined as
hepatitis B surface antigen [HBsAg] reactive) or known infection with hepatitis C
(defined as detectable HCV RNA via qualitative nucleic acid testing). Note -this
exclusion criterion does not apply to participants with HCC. For participants with HCC
only: participants with past or ongoing HCV infection will be eligible for the study
but must have completed their treatment at least 1 month prior to starting study
intervention and their HCV viral load has to be below the limit of quantification.
Participants who are HCV antibody (HCVAb positive but HCV RNA negative, due to prior
treatment or natural resolution, will be eligible. Participants with past or
controlled ongoing HBV will be eligible as long as their HBV viral load is less than
500 IU/mL prior to first dose of study drug. Participants on active HBV therapy with
viral loads under 100 IU/mL should stay on the same therapy throughout study
intervention.
8. Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases and/or carcinomatous meningitis, with the exception of participants with
GBM. Participants with previously treated metastases may participate provided they are
radiologically stable for at least 4 weeks by repeat imaging performed during study
screening, clinically stable, and without requirement for steroid treatment above
10mg/day (prednisone) for at least 28days prior to the first dose of study
intervention. An MRI brain scan for all participants with stable brain metastases at
screening (CT scan will be allowed if MRI is contraindicated).
9. Participants with clinically significant, progressing malignant ascites except for
those with ovarian tumours•Participants with known history of non-infectious
pneumonitis, myocarditis, or nephritis•Signs and symptoms of heart failure within the
last 12 months characterised as greater than New York Heart Association (NYHA) Class I
or other clinically significant cardiac abnormalities (such as myocardial infarction)
including stable abnormalities.
10. Major surgery within the last 30 days prior to study treatment initiation.
Participants must have recovered adequately from the procedure and/or any
complications from the surgery prior to starting study intervention.
11. Participants with history of solid organ or haematological
transplantation•Participants with sepsis, ineffective biliary drainage with or without
cholangitis, obstructive jaundice or encephalopathy at screening visit or within the
last 2weeks prior to study treatment initiation, whichever is earlier
12. Evidence of spontaneous bacterial peritonitis or renal failure, or allergic reaction
at screening visit or within the last 2 weeks prior to study treatment initiation,
whichever is earlier•Pregnant or lactating women
13. Received systemic corticosteroids and other immunosuppressants in the 4 weeks prior to
enrolment into the study (please see note on exception details in Section 6.3.1).
14. Received live (attenuated) vaccine in the 30 days prior to first dose of study
drug.Live vaccines include, but are not limited to: measles, mumps, rubella,
varicella/zoster chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG),
and typhoid vaccine. Seasonal influenza and COVID-19 vaccines for injection are
generally inactive/not viablevirus vaccines and are allowed; however, intranasal
influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
15. Active or prior documented autoimmune or inflammatory disorders (including
inflammatory bowel disease [e.g., colitis or Crohn's disease]requiring
immunosuppressive treatment, diverticulitis [with the exception of diverticulosis],
systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome
[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis,
hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
- Participants with vitiligo or alopecia.
- Participants with hypothyroidism (e.g., following Hashimoto syndrome) euthyroid
on hormone replacement.
- Any chronic skin condition that does not require systemic therapy.
- Participants without active disease in the last 2 years may be included but only
after consultation with the study physician.
- Participants with coeliac disease controlled by diet alone.
16. Participants with an active infection requiring systemic therapy.
17. Known hypersensitivity to the active substance (pembrolizumab) or to any of the
excipients.
18. Any known additional malignancy requiring active treatment within the past 3 years.
Exceptions include early-stage cancers such carcinoma in situ or stage 1, such as
melanoma, basal cell carcinoma or squamous cell carcinoma of the skin, in situ
cervical cancer, or in situbreast cancer, which have been treated with curative
intent.
19. Any other condition (including psychiatric or substance abuse, known or suspected poor
compliance, etc.), therapy, or laboratory finding that, in the judgement of the
investigator, may affect the participant's ability to participate, fully follow the
protocol specific procedures, or is not in the best interest of the participant to
take part in the study.
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