Trial Outcomes & Findings for A Phase I/II Study of Intratumoral Injection of SD-101 (NCT NCT02254772)
NCT ID: NCT02254772
Last Updated: 2019-11-27
Results Overview
To determine the safety and tolerability of SD-101 (1 mg/week) and local low dose radiation plus escalating doses of subcutaneously (SC)-administered ipilimumab, the incidence of dose-limiting toxicities (DLT) will be assessed according to the following DLT definitions. Related adverse events (AEs) are toxicities. "Treatment" includes radiation therapy. * Grade 4 treatment-related AE * Any drug-related AE ≥ Grade 3, including injection site reaction * ≥ Grade 3 treatment-related clinical autoimmune reaction involving major organs (defined as liver, pancreas, lung, heart, kidney, bowel, bone marrow, eye, or central nervous system) which does not resolve to baseline or Grade 1 within 6 weeks * Treatment-related AE ≥ Grade 3 that persists despite adequate/maximal medical therapy and/or prophylaxis, EXCEPT * Treatment-related skin rash ≤ Grade 3, that does not require systemic steroid therapy or other immunosuppressive therapy OR * Grade 3 flu-like AEs * Uveitis ≥ Grade 2
COMPLETED
PHASE1/PHASE2
9 participants
Up to 10 weeks
2019-11-27
Participant Flow
Participant milestones
| Measure |
Treatment (SD-101 + Ipilimumab + Radiation)
Patients receive TLR9 agonist SD-101 via intratumoral injections; ipilimumab via intratumoral injection; and undergo radiation therapy on days 1 and 2.
|
|---|---|
|
Overall Study
STARTED
|
9
|
|
Overall Study
COMPLETED
|
7
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Treatment (SD-101 + Ipilimumab + Radiation)
Patients receive TLR9 agonist SD-101 via intratumoral injections; ipilimumab via intratumoral injection; and undergo radiation therapy on days 1 and 2.
|
|---|---|
|
Overall Study
Ineligible
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
A Phase I/II Study of Intratumoral Injection of SD-101
Baseline characteristics by cohort
| Measure |
Treatment (SD-101 + Ipilimumab + Radiation)
n=9 Participants
Patients receive TLR9 agonist SD-101 via intratumoral injections; ipilimumab via intratumoral injection; and undergo radiation therapy on days 1 and 2.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
6 Participants
n=99 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Up to 10 weeksPopulation: Only the starting dose level of 10 mg ipilimumab plus SD-101 (1 mg/week) was evaluated. The dose level of ipilimumab could not be escalated due to inability to obtain a higher concentration of ipilimumab.
To determine the safety and tolerability of SD-101 (1 mg/week) and local low dose radiation plus escalating doses of subcutaneously (SC)-administered ipilimumab, the incidence of dose-limiting toxicities (DLT) will be assessed according to the following DLT definitions. Related adverse events (AEs) are toxicities. "Treatment" includes radiation therapy. * Grade 4 treatment-related AE * Any drug-related AE ≥ Grade 3, including injection site reaction * ≥ Grade 3 treatment-related clinical autoimmune reaction involving major organs (defined as liver, pancreas, lung, heart, kidney, bowel, bone marrow, eye, or central nervous system) which does not resolve to baseline or Grade 1 within 6 weeks * Treatment-related AE ≥ Grade 3 that persists despite adequate/maximal medical therapy and/or prophylaxis, EXCEPT * Treatment-related skin rash ≤ Grade 3, that does not require systemic steroid therapy or other immunosuppressive therapy OR * Grade 3 flu-like AEs * Uveitis ≥ Grade 2
Outcome measures
| Measure |
Treatment (SD-101 + Ipilimumab + Radiation)
n=7 Participants
Patients receive TLR9 agonist SD-101 via intratumoral injections; ipilimumab via intratumoral injection; and undergo radiation therapy on days 1 and 2.
|
|---|---|
|
Number of Dose-limiting Toxicity (DLT) Events of Ipilimumab Plus a Fixed Dose of SD-101 (1 mg/Week)
|
0 Dose-limiting toxicity events
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: Note that 1 participants initially experienced a partial response (PR), but later had progressive disease (PD).
Tumor response was assessed per the Cheson Criteria for low-grade B-cell lymphomas. Complete Response (CR) - No evidence disease. Partial Response (PR) - Regression of measurable disease with no new sites Progressive Disease (PD) - Any new lesion or increase by ≥ 50% of any previously-involved site after treatment nadir. Stable Disease (SD) - Any status that is not CR; PR; or PD. See references (Cheson BD, et al. J Clin Oncol. Apr 1999;17(4):1244. PubMed ID 10561185.
Outcome measures
| Measure |
Treatment (SD-101 + Ipilimumab + Radiation)
n=7 Participants
Patients receive TLR9 agonist SD-101 via intratumoral injections; ipilimumab via intratumoral injection; and undergo radiation therapy on days 1 and 2.
|
|---|---|
|
Tumor Response
Complete Response (CR)
|
0 Participants
|
|
Tumor Response
Partial Response (PR)
|
1 Participants
|
|
Tumor Response
Stable Disease (SD)
|
1 Participants
|
|
Tumor Response
Progressive Disease (PD)
|
6 Participants
|
SECONDARY outcome
Timeframe: Up to 2 yearsPopulation: 1 participant had stable disease, but did not provide a final follow-up at 2 years.
Tumor progression was assessed as any new lesion or increase by ≥ 50% of any previously-involved site after treatment nadir.
Outcome measures
| Measure |
Treatment (SD-101 + Ipilimumab + Radiation)
n=6 Participants
Patients receive TLR9 agonist SD-101 via intratumoral injections; ipilimumab via intratumoral injection; and undergo radiation therapy on days 1 and 2.
|
|---|---|
|
Median Time to Progression (TTP)
|
3.33 Months
Interval 0.53 to 12.32
|
Adverse Events
Treatment (SD-101 + Ipilimumab + Radiation)
Serious adverse events
| Measure |
Treatment (SD-101 + Ipilimumab + Radiation)
n=9 participants at risk
Patients receive TLR9 agonist SD-101 via intratumoral injections; ipilimumab via intratumoral injection; and undergo radiation therapy on days 1 and 2.
|
|---|---|
|
Infections and infestations
Neutropenia
|
11.1%
1/9 • Number of events 1 • 2 years
|
|
Infections and infestations
Sepsis
|
11.1%
1/9 • Number of events 1 • 2 years
|
Other adverse events
| Measure |
Treatment (SD-101 + Ipilimumab + Radiation)
n=9 participants at risk
Patients receive TLR9 agonist SD-101 via intratumoral injections; ipilimumab via intratumoral injection; and undergo radiation therapy on days 1 and 2.
|
|---|---|
|
Infections and infestations
Neutropenia
|
11.1%
1/9 • Number of events 1 • 2 years
|
|
Blood and lymphatic system disorders
Pancytopenia
|
11.1%
1/9 • Number of events 1 • 2 years
|
|
Blood and lymphatic system disorders
Anemia
|
11.1%
1/9 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Nausea
|
11.1%
1/9 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Diarrhea
|
11.1%
1/9 • Number of events 1 • 2 years
|
|
Gastrointestinal disorders
Bloating
|
22.2%
2/9 • Number of events 2 • 2 years
|
|
Gastrointestinal disorders
Dysphagia
|
11.1%
1/9 • Number of events 1 • 2 years
|
|
Metabolism and nutrition disorders
Anorexia
|
11.1%
1/9 • Number of events 1 • 2 years
|
|
General disorders
Fatigue
|
100.0%
9/9 • Number of events 13 • 2 years
|
|
General disorders
Fever
|
55.6%
5/9 • Number of events 5 • 2 years
|
|
General disorders
Injection site reaction
|
55.6%
5/9 • Number of events 5 • 2 years
|
|
General disorders
Swelling
|
33.3%
3/9 • Number of events 3 • 2 years
|
|
General disorders
Chills
|
44.4%
4/9 • Number of events 4 • 2 years
|
|
General disorders
Flu Like Symptoms
|
11.1%
1/9 • Number of events 1 • 2 years
|
|
General disorders
Malaise
|
11.1%
1/9 • Number of events 1 • 2 years
|
|
Injury, poisoning and procedural complications
Bruising
|
33.3%
3/9 • Number of events 3 • 2 years
|
|
Investigations
Increased Creatinine
|
11.1%
1/9 • Number of events 1 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
100.0%
9/9 • Number of events 10 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
100.0%
9/9 • Number of events 9 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.1%
1/9 • Number of events 1 • 2 years
|
|
Nervous system disorders
Headache
|
100.0%
9/9 • Number of events 11 • 2 years
|
|
Skin and subcutaneous tissue disorders
Induration
|
22.2%
2/9 • Number of events 2 • 2 years
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
3/9 • Number of events 3 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
33.3%
3/9 • Number of events 3 • 2 years
|
|
Reproductive system and breast disorders
Cough
|
33.3%
3/9 • Number of events 3 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
11.1%
1/9 • Number of events 1 • 2 years
|
Additional Information
Ronald Levy, MD, Professor of Medicine
Stanford Univeristy Medical Center
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place