Primary: To characterize safety and tolerability of MIW815 (ADU-S100) given with PDR001 and identify recommended doses and schedule for future studies.Secondary: Anti-tumor activity. Pharmacodynamics (PD). Pharmacokinetics (PK).
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Iincidence and severity of (serious) adverse events, including changs in
laboratory parameters, vital signs, ECGs, incidence of DLT during the 1st
cycle.
Secondary outcome
Overall response rate, progression free survival, duration of response, disease
control rate, PK parameters. Antidrug antibodies. Tumor Infiltrating
lymphocytes in (non-)injected lesions.
Background summary
The recent development of agents that enhance anti-tumor immunity is rapidly
changing the treatment of cancer. Inhibitors of the PD-1/PD-L1 interaction,
like PDR001, are well tolerated and active across a remarkable range of cancer
types. However, they are not efficacious in all tumors or all patients and
exploration of combinations are warranted. STING agonists have the potential to
augment, initiate, or awaken the initial anti-cancer response.
Pre-clinical data demonstrated significant enhanced local and distal anti-tumor
activity following intratumoral administration of MIW815 (ADU-S100). Local and
systemic anti-tumor efficacy required activation of STING-responsive cells in
the tumor microenvironment, as SC injection in sites distal from tumor masses
was not effective.
This is a Phase Ib study with the primary aim to determine if PDR001 can be
safely combined with MIW815 (ADU-S100) and to identify the doses and schedule
appropriate for further study.
Study objective
Primary:
To characterize safety and tolerability of MIW815 (ADU-S100) given with PDR001
and identify recommended doses and schedule for future studies.
Secondary:
Anti-tumor activity. Pharmacodynamics (PD). Pharmacokinetics (PK).
Study design
Phase Ib, multi-center, open-label dose escalation and dose expansion study of
MIW815 in combination with PDR001.
Two different dosing schedules of MIW815 (cycles of 4 weeks)
1. Intratumoral injections on day 1, 8 and 15 of each cycle plus 400 mg PDR001
IV on day 1 of each cycle.
2. Intratumoral injections on day 1 of each cycle plus 400 mg PDR001 IV on day
1 of each cycle.
will be explored in groups with accessible cutaneous or subcutaneous lesions.
A dose confirmation group (fixed dose) will explore intratumoral injection of
viscerally located lesions at a later stage during the study if biological
activity is seen in the 2nd dosing group (once per 4 weeks). If biological
activity is seen in the dose confirmation group, a dose expansion group will be
opened for visceral lesions.
Approx.140 subjects (40 dose escalation part, 100 expansion part).
Intervention
MIW815 (intra tumoral) - increasing dose. 2 schedules
A) day 1-8 and 15 in a 4-week cycle
B) day 1 in a 4-week cycle
PDR001: fixed dose every 4 weeks, administered intravenously in 100ml glucose
Study burden and risks
Risk: Adverse effects of MIW815 in combination with PDR001.
Burden: Cycles of 4 weeks. 3 visits per cycle.
MIW815: 3 or 1 intratumoral injection(s) 0,5-4,0 mL per cycle.
PDR001: 1 infusion (250 mL) per cycle.
Physical examination: once per cycle.
Blood tests (20-70 mL/occasion): 1st day of every cycle (cycle 1-2: 3 times).
Urine testing: once.
Pregnancy test: every cycle and every month during safety follow-up.
ECG: 4 times.
Tumor measurements: baseline, cycle 3 and every 8 weeks thereafter up to cycle
11 and every 3rd cycle thereafter. During follow up for progression every 8-12
weeks.
Tumor biopsy: twice.
Risks related to assessments as blood draw, infusion, imaging
Haaksbergweg 16
Amsterdam 1101 BX
NL
Haaksbergweg 16
Amsterdam 1101 BX
NL
Listed location countries
Age
Inclusion criteria
1. Male and female *18 years of age.
2. Measurable disease as determined by RECIST v1.1 (for solid tumors) or Cheson
2014 criteria (for lymphoma).
3. At least two sites of disease amenable to biopsy, and willing to undergo new
tumor biopsy at screening and during therapy. See protocol page 30-31 for
details.
4. Dose escalation part: Advanced/metastatic solid tumors or lymphomas that
have progressed despite standard therapy or where standard therapy is not
tolerated, for whom no standard therapy exists or for whom standard therapy is
not reasonably effective.
5. Dose expansion part: Melanoma patients with accessible cutaneous or
subcutaneous lesions, who have relapsed or progressed after responding to a
PD-1 inhibitor or who are refractory to PD-1 Inhibitors, HNSCC or patients with
other accessible cutaneous or subcutaneous solid tumors and lymphomas, that
have progressed despite standard therapy or are intolerant of standard therapy,
for whom no standard therapy exists or for whom standard therapy is not
reasonably effective. In addition, patients with injectable visceral lesions
who have MSS CRC or other solid tumors with accessible visceral lesions, who
have progressed despite standard therapy or are intolerant of standard therapy,
for whom no standard therapy exists or for whom standard therapy is not
reasonably effective.
6. ECOG performance status 0-1
Exclusion criteria
1. Patients who require immediate local palliative measures such as XRT or
surgery.
2. Symptomatic or untreated leptomeningeal disease.
3. Symptomatic -CNS metastases, see protocol page 31 for details.
4. Laboratory abnormalities:
- Creatinine > 1.5 x upper limit of normal (ULN)
- Total bilirubin > 1.5 x ULN (except for Gilbert*s syndrome > 3.0 x ULN)
- ALT and AST (liver) > 3 x ULN (except when livermetastasis > 5 x ULN_
- Absolute neutrophil count < 1.0 x 109/L
- Platelet count < 75 x 109/L, except for patients in Group C: platelet count <
100 x 109/L
- INR > 1.5 x ULN and/or aPTT > 1.5 x ULN, except for patients in Group C: INR
and aPTT must be normal
- Hemoglobin (Hgb) < 9 g/dL (5,59 mmol/l)
- Potassium, magnesium, calcium or phosphate > grade 1 using CTCAE v4.03
5. Impaired cardiac function or clinically significant cardiac disease, see
protocol page 42 for details.
6. Active, known or suspected autoimmune disease or a documented history of
autoimmune disease, see protocol page 43 for details.
7. Active infection requiring systemic antibiotic therapy.
8. Cytotoxic or targeted antineoplastics within 14 days prior to the first dose
of study treatment, see protocol page 43 for details.
9. Systemic chronic steroid therapy (* 10mg/day prednisone or equivalent) or
any immunosuppressive therapy 7 days prior to start of study treatment.
10. Use of any live vaccines against infectious diseases within 4 weeks of
initiation of study treatment.
11. Use of G-CSF and comparable, see protocol page 43/44 for details.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-000707-25-NL |
| ClinicalTrials.gov | NCT03172936 |
| CCMO | NL61921.031.17 |