A Phase 2 study intended to see efficacy of tilsotolimod in combination with immunotheraphy
drugs ipilimumab and nivolumab in different solid tumors.
This is a Phase 2, open-label, global, multi-center, multicohort study of intratumoral
tilsotolimod in combination with nivolumab and ipilimumab for the treatment of specific solid
Main Inclusion Criteria:
1. Subject ≥ 18 years of age (males and females)
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 minimum life
expectancy ≥ 4 months, adequate organ functions, and ≥1 lesion accessible for
intratumoral injection and biopsy(ies).
3. Women of child bearing potential (WOCBP) and men with WOCBP partners must agree to use
effective contraception methods as defined I n the clinical study protocol.
Inclusion Criteria (RM SCCHN IO Naïve):
1. Histologically and/or cytologically confirmed recurrent or metastatic, PD(L)1 negative
or positive SCCHN (oral cavity, oropharynx, larynx, or hypopharynx) that is not
amenable to curative therapy (by surgery or radiation with or without chemotherapy).
2. At least 1 measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1, minimum 10 mm except lymph nodes (minimum short axis 15 mm). Target lesions may
be in a previously irradiated field if there is documented (radiographic) disease
progression in that site after the completion of radiation therapy.
Inclusion Criteria ( MSS CRC IO Naïve)
1. Histologically confirmed advanced, metastatic, or progressive MSS CRC based on either
an analysis of tissue from a prior biopsy or based on tissue from a new biopsy.
Subject's microsatellite/MMR status should be known.
2. Received at least two prior regimens of therapy for advanced or metastatic CRC
including fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens. Subjects who
relapse within 6 months of adjuvant chemotherapy composed of oxaliplatin and a
fluoropyrimidine will have their adjuvant therapy count as one prior regimen.
3. Documentation of radiologic progression by Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1 during or after previous chemotherapy.
Main Exclusion Criteria:
1. Subject must have completed or completely discontinued any previous cancer-related
treatments before enrollment with necessary windows and wash out periods as defined in
the clinical study protocol.
2. History of interstitial lung disease, pneumonitis, known or suspected autoimmune
diseases (unless for specific diseases as defined in protocol) or human
immunodeficiency virus (HIV) infection.
3. Prior therapy with TLR9 agonist, excluding topical agents.
4. Known hypersensitivity to any study drug component.
5. Prior immune-mediated AE of intensity Grade ≥ 3.
6. Subject with another primary malignancy that has not been in remission for at least 3
years except for non-melanoma skin cancer, curatively treated localized prostate
cancer with non-detectable prostate specific antigen, cervical carcinoma in situ on
biopsy, or thyroid cancer (except anaplastic).
7. Active systemic infections requiring antibiotics, active Hepatitis A, B or C
8. Women who are breast feeding or pregnant.
9. Prior anaphylactic or other severe infusion reaction associated with human antibody
administration that cannot be managed by standard supportive measurements.
10. Presence of unstable central nervous system disease involvement
11. Subject with unstable and impaired cardiac function or clinically significant cardiac
disease per Investigator's clinical judgment.
12. Has received live attenuated vaccine 30 days before first study dose.
Exclusion Criteria ((RM SCCHN IO Naïve):
1. Subject with squamous cell carcinoma of any other primary anatomic location in the
head and neck (eg, paranasal cavity), subjects with squamous cell carcinoma of unknown
primary, and subject with nonsquamous histologies of head and neck tumors.
2. Subject who received prior systemic therapy for SCCHN in the recurrent or metastatic
setting (exception: subject with persistent disease after treatment in locally
3. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent
directed to another stimulatory or co-inhibitory T-cell receptor in approved or
4. The only lesion available for injection is in close proximity to or invading a major
blood vessel (such as the carotid artery).
Exclusion Criteria (MSS CRC IO Naïve):
1. Prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed cell death
ligand-1 (PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory
or co-inhibitory T-cell receptor in an approved or experimental setting.
2. Subjects with BRAF V600E mutations.
3. Subjects with a history of immune-mediated colitis.