This is an open-label, single-arm study in patients with superficial advanced solid tumors
accessible for injection (cutaneous, subcutaneous, lymph node, or intramuscular tumors) and
who have either exhausted treatment options or are not eligible for, suitable for, or willing
to undergo such treatments.
This study aims to assess the safety and efficacy of LTX-315 in combination with the immune
checkpoint inhibitor (ICI) pembrolizumab in patients with superficial advanced solid tumors.
LTX-315 has been administered with pembrolizumab in a previous Phase 1/2 study (Study
C12-315-03), and there were clear indications that LTX-315 + pembrolizumab was a clinically
active combination. Furthermore, the addition of LTX-315 to pembrolizumab dosing did not
appear to increase the overall incidence or severity profile of toxicities.
The present study will document the preliminary efficacy, clinical safety, and tolerability
of LTX-315 in combination with pembrolizumab, in a dose and regimen that is considered to be
safe, in 2 cohorts of patients:
Cohort 1 will consist of patients with selected tumors that have an FDA-approved ICI
treatment and have progressed after prior anti-programmed death-1 (PD-1) or anti-programmed
death-ligand 1 (PD-L1) therapy, alone or in combination with systemic therapy.
Cohort 2 will consist of patients with tumors that do not have any FDA-approved ICI
treatment, and may or may not have received prior anti-PD-1 or anti-PD-L1 therapy. The
rationale for including this cohort is to test the ability of intratumoral injection of
LTX-315 to convert an immunologically "cold" tumor to "hot" by causing cytolysis within the
1. Have 1 of the following cancer types, confirmed histologically:
Cohort 1 (patients with selected tumors that have an FDA-approved ICI treatment and
have progressed after prior anti-PD-1 or anti-PD-L1 therapy, alone or in combination
with systemic therapy).
For patients who have refused prior standard-of-care treatment as indicated for their
specific tumor type, the patient's reason for refusing standard therapy for their
disease shall be clearly documented in the study electronic case report form (eCRF)
prior to study participation. All patients in Cohort 1 must have received anti-PD1 or
anti-PD-L1 in addition to complying with the relevant criteria below.
1. Melanoma - patients with unresectable or metastatic disease that is either
refractory to, or has relapsed following, at least 1 line of systemic therapy in
the metastatic setting. Melanoma patients with BRAF mutation who are eligible and
suitable for BRAF inhibitor therapy should have received specific BRAF inhibitor
therapy before enrolling in this study. Patients who have refused BRAF inhibitor
therapy are also eligible for the study.
2. Triple-negative breast cancer - patients with locally advanced or metastatic
triple-negative breast cancer expressing PD-L1 that is either refractory to, or
relapsed after, at least 2 prior standard courses of systemic therapy, as
described below, OR the patient has refused or is not eligible/suitable for such
i. Patients should have received at least 2 lines of chemotherapy (in the metastatic
setting) containing 1 or more of the following agents: doxorubicin, epirubicin,
pegylated liposomal doxorubicin, docetaxel, paclitaxel, albumin-bound paclitaxel
(Abraxane), atezolizumab, gemcitabine, vinorelbine, vinblastine, capecitabine,
ixabepilone (Ixempra) eribulin, platinum.
ii. If a patient has a germline BRCA mutation and has received a PARP inhibitor, this
will be counted as 1 line of chemotherapy.
c. Non-small cell lung cancer (NSCLC) - patients with disease that is either
refractory to at least 2 lines of chemotherapy (in the metastatic setting) OR the
patient has refused or is not eligible/suitable for such therapy.
i. One line should be a platinum-based regimen.
ii. One line should be in accordance with the National Comprehensive Cancer Network
(NCCN)-recommended treatments by mutation.
d. Urothelial carcinoma - patients with locally advanced or metastatic disease that is
either refractory to at least 2 lines of systemic therapy (in the metastatic setting)
OR the patient has refused or is not eligible/suitable for such therapy. One line
should be a cisplatin-based regimen if patient was eligible for cisplatin-based
e. Microsatellite instability-high or deficient mismatch repair (dMMR) solid cancer -
patients with unresectable or metastatic disease which has progressed following
systemic therapy (in the metastatic setting). Patients with colorectal cancer must
have received fluoropyrimidine, oxaliplatin, and irinotecan.
f. Gastric or gastroesophageal junction adenocarcinoma cancer expressing PD-L1 -
patients with recurrent, locally advanced, or metastatic disease expressing PD-L1
(combined positive score [CPS] ≥1) which is either refractory to the following
therapies (in the metastatic setting) OR the patient has refused or is not
eligible/suitable for such therapy:
i. Two or more lines of chemotherapy including at a minimum both fluoropyrimidine- and
platinum-containing chemotherapy, and
ii. If appropriate, HER2/neu-targeted therapy
g. Hepatocellular carcinoma - patients who are either refractory to sorafenib (in the
metastatic setting) OR the patient has refused or is not eligible/suitable for such
h. Renal cell carcinoma - patients with advanced disease that has progressed after at
least one line of systemic therapy (in the metastatic setting).
i. Merkel cell carcinoma - patients with metastatic Merkel cell carcinoma who have
progressive disease after at least 1 line of systemic therapy (in the metastatic
j. Head and neck squamous cell carcinoma - patients with refractory, recurrent, or
metastatic disease who have had radiotherapy given with curative intent and received
the following treatments (unless ineligible or patient has refused the treatment):
i. At least 1 course of platinum-based chemotherapy for recurrence or metastatic
ii. At least 1 course of afatinib.
k. Small cell lung cancer - patients who are either refractory to at least 1 line of
platinum-based chemotherapy and 1 other prior regimen (in the metastatic setting), OR
patients who have refused or are not eligible/suitable for such therapy.
l. Squamous cell carcinoma of esophagus expressing PD-L1 (CPS ≥10) - patients with
recurrent, locally advanced, or metastatic disease that is either refractory to at
least 1 prior line of systemic therapy (in the metastatic setting) OR patients who
have refused or are not eligible/suitable for such therapy.
m. Cervical cancer expressing PD-L1 (CPS ≥1) - patients with recurrent or metastatic
disease that is either refractory to, or progressed after, at least one line of
systemic therapy (in the metastatic setting).
Cohort 2 (patients with tumors that do not have any FDA-approved ICI treatment, and
may or may not have received prior anti-PD-1 or anti-PD-L1 therapy).
n. Patients in Cohort 2 should have progressed after standard-of-care anticancer
For Cohorts 1 and 2:
- The patients should have had radiologically progressive disease after the most
recent line of systemic therapy.
- Anti-PD-1 or anti-PD-L1 need not be the most recent line of therapy.
2. Disease that is not amenable to further radiotherapy or surgery for cancer treatment.
3. Have at least 1 superficial, nonvisceral tumor lesion accessible for injection via
cutaneous, subcutaneous, or intramuscular route. Note, lymph nodes with metastatic
disease may be selected for injection if they are superficial, but not if deep-seated;
visceral lesions must not be selected for injection. The lesion must not be located
close to airways, defined as close enough to jeopardize the patient's safety, in the
opinion of the investigator, in the event of a local reaction to LTX-315 injection
(for example, if such a reaction has the potential to interfere with swallowing or
result in hemorrhaging into the airways). The size of the lesion(s) selected for
injection must be ≥0.5 cm, and preferably ≤3 cm in the longest diameter. For larger
lesions, approval from the sponsor and medical monitor is needed prior to enrollment.
4. At least 1 measurable tumor lesion evaluable according to RECIST version 1.1 that is
not planned to be injected with LTX-315. The location of this noninjected tumor may be
superficial, deep-seated, or visceral.
5. Have a life expectancy ≥3 months.
6. Are males or females aged 18 years or older.
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
8. Have an LVEF that is above the institution's lower limit of normal (by echo scan
9. Meet the following laboratory requirements:
1. Absolute neutrophil count ≥1.5 × 109/L
2. Absolute lymphocyte count that is above the institution's lower limit of normal
3. Platelet count ≥75 × 109/L
4. Hemoglobin ≥9.0 g/dL
5. Prothrombin time/international normalized ratio ≤ the institution's upper limit
of normal (ULN)
6. Serum total bilirubin ≤ULN (total bilirubin ≤2 × ULN if associated with
hepatobiliary metastases or Gilbert's syndrome)
7. Aspartate aminotransferase and alanine aminotransferase ≤2.5 × ULN (≤5 × ULN if
liver metastasis present or in case of hepatocellular carcinoma)
8. Calculated creatinine clearance ≥30 mL/min using Cockcroft-Gault formula.
10. Are willing and able to comply with the protocol and agree to return to the clinical
site for Follow-up Visits and examinations.
11. Are willing to undergo tumor biopsy procedures.
12. Are fully informed about the study and have signed the informed consent form.
13. Are willing to use contraceptive measures as prescribed by the protocol. Female
patients of childbearing potential and their partners who are sexually active must
agree to the use of 2 highly effective forms of contraception starting from the
screening visit, throughout their participation in the study, and for at least 120
days after their last dose of pembrolizumab or at least 180 days after their last dose
of LTX-315, whichever is longer. Male patients with partners who are pregnant or of
childbearing potential must use a barrier method of contraception starting from the
screening visit, throughout their participation in the study and for at least 120 days
after their last dose of pembrolizumab or at least 180 days after their last dose of
LTX-315, whichever is longer. A woman is considered of childbearing potential, ie,
fertile, following menarche and until becoming postmenopausal unless permanently
14. Female patients must not be pregnant or breastfeeding. Female patients of childbearing
potential must have a negative pregnancy test result during screening and at Day 1.
1. Excessive tumor burden, in the opinion of the investigator.
2. Known bone-only or brain metastases.
3. Have a history of cerebrovascular or cardiac disorders (eg, Class III or IV New York
Heart Association cardiac failure) and would be at particular risk of sequelae
following a short hypotensive episode.
4. Have a marked baseline prolongation of QT interval/QTcF (eg, repeated demonstration of
a QTc interval >480 ms [CTCAE Grade 1]).
5. Are currently taking immunosuppressive agents (see Appendix for examples). Patients
who require corticosteroids should have been on a stable dose (up to 10 mg daily
prednisone or equivalent) for at least 2 weeks prior to study drug administration.
Topical corticosteroids are also permitted.
6. Have a history of systemic autoimmune disease requiring anti-inflammatory or
immunosuppressive therapy within 3 months prior to Day 1, with the following
1. Patients with a history of autoimmune thyroiditis are eligible provided the
patient requires only thyroid hormone replacement therapy and disease has been
stable for ≥1 year.
2. Patients with well-controlled type I diabetes (in the opinion of the
investigator) are eligible.
7. Patients who are allergic or have hypersensitivity to chlorpheniramine or equivalent
H1 antagonist, cimetidine or equivalent H2 antagonist, or montelukast.
8. Have a history of severe hypersensitivity to another monoclonal antibody; are
receiving immunosuppressive therapy; have a history of severe immune-related adverse
reaction from treatment with a monoclonal antibody, defined as any Grade ≥3 toxicity
requiring corticosteroid treatment (>10 mg/day prednisone or equivalent) for >12
9. Have had pneumonitis Grade ≥3 in the past.
10. Have a known hypersensitivity to pembrolizumab or any of the excipients listed in the
11. Have any other serious illness or medical condition, such as, but not limited to:
1. Uncontrolled infection or infection requiring systemic antibiotics
2. Uncontrolled cardiac failure: Class III or IV New York Heart Association
3. Uncontrolled systemic or gastrointestinal inflammatory conditions
4. Known bone marrow dysplasia
5. History of positive tests for HIV/acquired immunodeficiency syndrome or active
hepatitis B or C (based on serology); positive serology will be confirmed by a
viral load test. Patients with treated HIV and a viral load test result
consistent with treated HIV, as well as patients with treated hepatitis B or C
with an undetectable viral load test result, are eligible.
6. History of or current mastocytosis.
12. Have received external radiotherapy or cytotoxic chemotherapy within 4 weeks prior to
Day 1 or have not recovered (to NCI-CTCAE Grade ≤1; alopecia of any grade is allowed,
and peripheral neuropathy of up to Grade 2 is allowed) from AEs due to such agents
being administered more than 4 weeks prior to Day 1. Palliative radiotherapy to
nontarget lesions within 4 weeks prior to Day 1 is allowed.
13. Have received cancer immunotherapy within 4 weeks prior to Day 1 or have not recovered
from AEs (to NCI-CTCAE Grade ≤1) due to such agents being administered more than 4
weeks prior to Day 1.
14. Have received an investigational drug within 4 weeks prior to Day 1 or are scheduled
to receive one during the treatment or post-treatment periods.
15. Are expected to need any other anticancer therapy or immunotherapy to be initiated
during the study period.