Solid Tumor, Adult
Conditions
Brief summary
Open-label, dose escalation (Phase I) and dose expansion (Phase IIA) study of patients receiving intra-tumoral IMSA101 alone or in combination with an immune checkpoint inhibitor (ICI) (Phase I and II)
Detailed description
This is an open-label, dose escalation (Phase I), and dose expansion (Phase IIA) study designed to evaluate safety and efficacy of IMSA101 alone or in combination with an ICI (Phase I and II). Therefore, the study will be conducted in 2 phases. The dose of IMSA101 in Phase IIA will be based on the monotherapy and combination Recommended Phase 2 Doses (RP2Ds) from Phase I. The following methodology applies to all patients (unless otherwise indicated): * Pre-treatment screening radiographic tumor assessments will be collected within 30 days prior to initial dose for all patients. Photographic assessments for cutaneously-accessible lesions will be performed as detailed in a separate photography manual. * Treatment cycles will be 28 days in duration with lesions injected weekly on Day 1 for the first three weeks of Cycle 1 and then every 2 weeks during cycles 2 and beyond. * A single pre-defined lesion/lesion site (longest diameter ≥ 10 mm and ≤ 35 mm) shall be injected throughout study duration, if possible. Where the original injection site is considered by the investigator to become inaccessible, a second lesion/lesion site shall be selected as a replacement and this shall be used henceforth so long as it is considered accessible. Subsequent injection sites shall be replaced when they are considered inaccessible. * Where no remaining accessible lesions are present and where benefit of IMSA101 therapy is, in the opinion of the investigator, being derived by the patient, continued injections of IMSA101 into the vicinity of an inaccessible lesion or, in the case that a lesion can no longer be radiographically visualized, into the last known location of the non-visible lesion shall be allowed. * Patients will be admitted to the hospital for observation overnight following IT injection with IMSA101 on Day 1 of Cycle 1. Patients will be followed throughout the study for drug tolerability and safety by collection of clinical and laboratory data, including information on adverse events (AEs) using CTCAE v5.0 criteria, serious adverse events (SAEs), DLTs, concomitant medications, vital signs, and electrocardiograms (ECGs). * Patients will be assessed for anti-tumor efficacy based on radiographic assessments and if applicable, photographic tumor assessments, and analysis of Objective Response Rate (ORR), Time to Progression (TTP), and Progression Free Survival (PFS) using RECIST criteria (Appendix 13.2) at screening and the end (≤ 7 days) of even numbered cycles (Cycle 2, Cycle 4, etc.) after the first dosing.
Interventions
DRUGIMSA101
IMSA101 administered by intra-tumoral (IT) injection on Day 1 of Weeks 1, 2, and 3 for Cycle 1 and on Day 1 of Weeks 1 and 3 for all subsequent cycles.
Administered according to product label
DRUGImmuno-oncology (IO) therapy
Administered according to product label
Sponsors
ImmuneSensor Therapeutics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase I includes a monotherapy arm and an immune checkpoint inhibitor (ICI) combination therapy arm Phase II includes three arms, Arm A monotherapy, Arm B immuno-oncology (IO) combination therapy, Arm C IO combination therapy
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Signed informed consent and mental capability to understand the informed consent 2. Male or female patients \> 18 years of age 3. Histologically or cytologically documented locally advanced or metastatic solid tumor malignancies refractory to or otherwise ineligible for treatment with standard-of-care agents/regimens, including but not limited to: * Malignant melanoma * Hormone receptor negative breast cancer * Gastro-esophageal cancer * Non-small cell lung cancer * Head and neck cancer * Hepatoma * Renal cell carcinoma 4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 5. Evaluable or measurable disease as follows: * A minimum of 3 RECIST-evaluable lesions: one that is suitable for injection and biopsied; one non-injected that will be biopsied for abscopal effect; and one measurable lesion that will be followed for response only. * Injectable tumors shall be accessed by intralesional (cutaneous) or percutaneous injection only, including those lesions that are visible, palpable, or detectable by standard radiographic or ultrasound methods. Neither surgical procedures nor endoscopically-guided injections including those to endobronchial, endoluminal, or endosinusial spaces shall be allowed. While no anatomic locations are required or disallowed, lesions selected for intratumoral injection must, in the opinion of the investigator: * Not be immediately adjacent to blood vasculature or other physiologic landmarks in such a way that will accrue undue safety risk to the patient * Have longest diameter ≥ 10 mm and ≤ 50 mm * Be fully efficacy evaluable per RECIST v1.1 criteria 6. Life expectancy \> 3 months (Phase I) and \> 6 months (Phase IIA) 7. ECG without evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the investigator 8. Acceptable organ and marrow function as defined below: * Absolute neutrophil count \> 1,500 cells/μL * Platelets \> 50,000 cells/μL * Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) * Aspartate aminotransferase (AST)/alanine transaminase (ALT) ≤ 2.5 times ULN. If liver metastases are present, AST/ALT \< 5 times ULN * Serum creatinine \< 1.5 mg/dL and a measured creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault formula * Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 times ULN 9. Women of child-bearing potential (defined as a female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months with an appropriate clinical profile at the appropriate age, e.g., greater than 45 years) must have a negative serum pregnancy test prior to first dose of study drug 10. Male and female patients with reproductive potential must agree to use two forms of highly effective contraception throughout the study 11. Phase I combination only: Demonstrated RECIST stable disease through ≥ 4 consecutive cycles of an approved PD-1 or PD-L1 targeted ICI with no Grade ≥ 3 CTCAE events considered by the investigator to be drug-related.
Exclusion criteria
1. Anti-cancer therapy within 4 weeks or \< 5 half-lives of the first dose of study drug. 2. Failure to recover to Grade 1 or less from clinically significant AEs due to prior anti-cancer therapy. 3. Known untreated brain metastases or treated brain metastases that have not been stable (scan showing no worsening of central nervous system (CNS) lesion\[s\] and no requirement of corticosteroids) ≥ 4 weeks prior to study enrollment 4. Baseline prolongation of QT/QTc interval (QTc interval \> 470) 5. Uncontrolled intercurrent illness (including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations) that in opinion of the investigator would limit compliance with study requirements 6. Women who are pregnant or breastfeeding 7. Phase I combination only: Prior tumor progression through PD-1 or PD-L1 targeted ICI therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities | Cycle 1 (28 days) of therapy | Highest dose level of IMSA101 at which no more than 1 out of 6 patients experienced a dose limiting toxicity (DLT) during the first cycle (28 days) of therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response | 9 months | The sum of number of patients with best overall response (complete response, partial response, stable disease or progressive disease) as per RECIST v1.1 until End of Treatment. Tumor response was evaluated at the end of each even numbered cycle (eg. Cycle 2, Cycle 4, etc.) until End of Treatment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Monotherapy 100 μg 100 μg of IMSA101 injected intra-tumorally weekly on Day 1 for the first 3 week cycles of Cycle 1, and then every 2 weeks during Cycles 2 and beyond. | 4 |
| Monotherapy 200 μg 200 μg of IMSA101 injected intra-tumorally weekly on Day 1 for the first 3 week cycles of Cycle 1, and then every 2 weeks during Cycles 2 and beyond. | 3 |
| Monotherapy 400 μg 400 μg of IMSA101 injected intra-tumorally weekly on Day 1 for the first 3 week cycles of Cycle 1, and then every 2 weeks during Cycles 2 and beyond. | 4 |
| Monotherapy 800 μg 800 μg of IMSA101 injected intra-tumorally weekly on Day 1 for the first 3 week cycles of Cycle 1, and then every 2 weeks during Cycles 2 and beyond. | 4 |
| Monotherapy 1200 μg 1200 μg of IMSA101 injected intra-tumorally weekly on Day 1 for the first 3 week cycles of Cycle 1, and then every 2 weeks during Cycles 2 and beyond. | 7 |
| Combination Therapy 800 μg 800 μg of IMSA101 injected intra-tumorally weekly on Day 1 for the first 3 week cycles of Cycle 1, and then every 2 weeks during Cycles 2 and beyond.
Plus an ICI administered as per product label. | 4 |
| Combination Therapy 1200 μg 1200 μg of IMSA101 injected intra-tumorally weekly on Day 1 for the first 3 week cycles of Cycle 1, and then every 2 weeks during Cycles 2 and beyond.
Plus an ICI administered as per product label. | 7 |
| Combination Therapy 2400 μg 2400 μg of IMSA101 injected intra-tumorally weekly on Day 1 for the first 3 week cycles of Cycle 1, and then every 2 weeks during Cycles 2 and beyond.
Plus an ICI administered as per product label. | 7 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Consent withdrawn | 1 | 0 | 0 | 0 | 2 | 0 | 1 | 1 |
| Overall Study | Continuing on expanded access | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Death | 0 | 0 | 1 | 2 | 1 | 0 | 1 | 0 |
| Overall Study | Patient in hospice | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Monotherapy 200 μg | Monotherapy 400 μg | Monotherapy 800 μg | Monotherapy 1200 μg | Combination Therapy 800 μg | Combination Therapy 1200 μg | Monotherapy 100 μg | Combination Therapy 2400 μg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 3 Participants | 3 Participants | 4 Participants | 3 Participants | 0 Participants | 1 Participants | 4 Participants | 18 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 7 Participants | 3 Participants | 3 Participants | 22 Participants |
| Age, Continuous | 53.7 years STANDARD_DEVIATION 2.08 | 66.5 years STANDARD_DEVIATION 4.12 | 64.8 years STANDARD_DEVIATION 6.95 | 65.0 years STANDARD_DEVIATION 14.29 | 74.0 years STANDARD_DEVIATION 11.34 | 50.3 years STANDARD_DEVIATION 10.89 | 56.5 years STANDARD_DEVIATION 12.01 | 63.0 years STANDARD_DEVIATION 21.53 | 61.4 years STANDARD_DEVIATION 14.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 3 Participants | 7 Participants | 3 Participants | 4 Participants | 3 Participants | 5 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 7 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants | 2 Participants | 5 Participants | 4 Participants | 4 Participants | 3 Participants | 6 Participants | 26 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 2 Participants | 5 Participants | 2 Participants | 3 Participants | 1 Participants | 6 Participants | 22 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 2 Participants | 4 Participants | 3 Participants | 1 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 | 1 / 4 | 2 / 4 | 1 / 7 | 0 / 4 | 1 / 7 | 0 / 7 |
| other Total, other adverse events | 4 / 4 | 3 / 3 | 4 / 4 | 3 / 4 | 7 / 7 | 4 / 4 | 7 / 7 | 7 / 7 |
| serious Total, serious adverse events | 2 / 4 | 1 / 3 | 2 / 4 | 3 / 4 | 1 / 7 | 1 / 4 | 5 / 7 | 5 / 7 |
Outcome results
Primary
Number of Participants With Dose-Limiting Toxicities
Highest dose level of IMSA101 at which no more than 1 out of 6 patients experienced a dose limiting toxicity (DLT) during the first cycle (28 days) of therapy.
Time frame: Cycle 1 (28 days) of therapy
Population: Number of patients who received at least 3 doses of IMSA101 in Cycle 1 and completed 4 weeks on study, or received at least 1 dose of IMSA101 and experienced a DLT during Cycle 1 per dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Monotherapy 100 μg | Number of Participants With Dose-Limiting Toxicities | 0 Participants |
| Monotherapy 200 μg | Number of Participants With Dose-Limiting Toxicities | 0 Participants |
| Monotherapy 400 μg | Number of Participants With Dose-Limiting Toxicities | 0 Participants |
| Monotherapy 800 μg | Number of Participants With Dose-Limiting Toxicities | 0 Participants |
| Monotherapy 1200 μg | Number of Participants With Dose-Limiting Toxicities | 0 Participants |
| Combination Therapy 800 μg | Number of Participants With Dose-Limiting Toxicities | 0 Participants |
| Combination Therapy 1200 μg | Number of Participants With Dose-Limiting Toxicities | 1 Participants |
| Combination Therapy 2400 μg | Number of Participants With Dose-Limiting Toxicities | 0 Participants |
Secondary
Best Overall Response
The sum of number of patients with best overall response (complete response, partial response, stable disease or progressive disease) as per RECIST v1.1 until End of Treatment. Tumor response was evaluated at the end of each even numbered cycle (eg. Cycle 2, Cycle 4, etc.) until End of Treatment.
Time frame: 9 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Monotherapy 100 μg | Best Overall Response | Progressive Disease | 4 Participants |
| Monotherapy 100 μg | Best Overall Response | Partial Response | 0 Participants |
| Monotherapy 100 μg | Best Overall Response | Complete Response | 0 Participants |
| Monotherapy 100 μg | Best Overall Response | Not Evaluable | 0 Participants |
| Monotherapy 100 μg | Best Overall Response | Stable Disease | 0 Participants |
| Monotherapy 200 μg | Best Overall Response | Partial Response | 0 Participants |
| Monotherapy 200 μg | Best Overall Response | Stable Disease | 0 Participants |
| Monotherapy 200 μg | Best Overall Response | Complete Response | 0 Participants |
| Monotherapy 200 μg | Best Overall Response | Not Evaluable | 0 Participants |
| Monotherapy 200 μg | Best Overall Response | Progressive Disease | 3 Participants |
| Monotherapy 400 μg | Best Overall Response | Stable Disease | 1 Participants |
| Monotherapy 400 μg | Best Overall Response | Partial Response | 0 Participants |
| Monotherapy 400 μg | Best Overall Response | Not Evaluable | 0 Participants |
| Monotherapy 400 μg | Best Overall Response | Complete Response | 0 Participants |
| Monotherapy 400 μg | Best Overall Response | Progressive Disease | 2 Participants |
| Monotherapy 800 μg | Best Overall Response | Stable Disease | 0 Participants |
| Monotherapy 800 μg | Best Overall Response | Complete Response | 0 Participants |
| Monotherapy 800 μg | Best Overall Response | Partial Response | 0 Participants |
| Monotherapy 800 μg | Best Overall Response | Progressive Disease | 2 Participants |
| Monotherapy 800 μg | Best Overall Response | Not Evaluable | 0 Participants |
| Monotherapy 1200 μg | Best Overall Response | Partial Response | 0 Participants |
| Monotherapy 1200 μg | Best Overall Response | Progressive Disease | 6 Participants |
| Monotherapy 1200 μg | Best Overall Response | Stable Disease | 0 Participants |
| Monotherapy 1200 μg | Best Overall Response | Not Evaluable | 0 Participants |
| Monotherapy 1200 μg | Best Overall Response | Complete Response | 0 Participants |
| Combination Therapy 800 μg | Best Overall Response | Partial Response | 0 Participants |
| Combination Therapy 800 μg | Best Overall Response | Stable Disease | 1 Participants |
| Combination Therapy 800 μg | Best Overall Response | Progressive Disease | 3 Participants |
| Combination Therapy 800 μg | Best Overall Response | Complete Response | 0 Participants |
| Combination Therapy 800 μg | Best Overall Response | Not Evaluable | 0 Participants |
| Combination Therapy 1200 μg | Best Overall Response | Stable Disease | 0 Participants |
| Combination Therapy 1200 μg | Best Overall Response | Progressive Disease | 4 Participants |
| Combination Therapy 1200 μg | Best Overall Response | Partial Response | 1 Participants |
| Combination Therapy 1200 μg | Best Overall Response | Complete Response | 0 Participants |
| Combination Therapy 1200 μg | Best Overall Response | Not Evaluable | 0 Participants |
| Combination Therapy 2400 μg | Best Overall Response | Complete Response | 0 Participants |
| Combination Therapy 2400 μg | Best Overall Response | Not Evaluable | 0 Participants |
| Combination Therapy 2400 μg | Best Overall Response | Progressive Disease | 3 Participants |
| Combination Therapy 2400 μg | Best Overall Response | Partial Response | 0 Participants |
| Combination Therapy 2400 μg | Best Overall Response | Stable Disease | 1 Participants |