Neoplasms, Advanced
Conditions
Brief summary
This was a non-randomized, open-label study of MK-1966 used in combination with SD-101 in the treatment of advanced malignancies. The study included an initial Dose Evaluation phase (Part A) to determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) by evaluating Dose Limiting Toxicities (DLTs) of four dose combinations of MK-1966 and SD-101. Following determination of the MTD/MAD, approximately 20 participants each were to be enrolled in two expansion cohorts (Parts B or C) to confirm/refine the MTD/MAD. The study was terminated by the Sponsor before enrollment into Part A concluded and before enrollment into Parts B and C began.
Interventions
BIOLOGICALMK-1966
MK-1966 administered as an intravenous (IV) infusion
DRUGSD-101
SD-101 administered as an intratumoral (IT) injection
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has a histologically- or cytologically-confirmed advanced malignancy that has progressed after standard-of-care therapy/treatments and there is no available therapy likely to convey clinical benefit * Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Has a life expectancy ≥ 6 months * Female participants must not be pregnant (negative urine or serum human chorionic gonadotropin test at screening and again within 72 hours prior to receiving the first dose of study therapy) * Female and male participants of reproductive potential must agree to use adequate contraception during the course of the study through 120 days after study the last dose of study therapy * Has ability to submit archived or fresh tumor sample during the screening period
Exclusion criteria
* Has had chemotherapy, radiation, or biological cancer therapy within 4 weeks prior to the first dose of study therapy, or who has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or better from the adverse events due to cancer therapeutics administered more than 4 weeks earlier * Has participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days of study start * Is expected to require any other form of antineoplastic therapy while on study * Is on chronic systemic steroid therapy in excess of replacement doses, or on any other form of immunosuppressive medication * Has a history of a malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for 5 years * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has had a severe hypersensitivity reaction to treatment with another monoclonal antibody * Has an active autoimmune disease that has required systemic treatment in past 2 years * Has an active infection requiring therapy * Has active, current pneumonitis, or a history of (non-infectious) pneumonitis that required steroids * Has had a prior stem cell or bone marrow transplant * Is positive for Human Immunodeficiency Virus (HIV) and/or Hepatitis B or C * Has known psychiatric disorder that would interfere with fulfilling the requirements of the study * Is a regular user of any illicit drugs or had a recent history of substance abuse * Has symptomatic ascites or pleural effusion * Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study * Has clinically significant heart disease that affects normal activities * Has had major surgery (requiring at least a 3 day hospital stay) in the past 28 days * Has received a live vaccine within 30 days prior to first dose of study therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Dose Limiting Toxicity (DLT) | From time of first dose of study drug to the end of Cycle 1. Each cycle was 21 days. (Up to 21 days) | The occurrence of any of the following toxicities during Cycle 1 (Days 1-21), if assessed by the Investigator to be possibly, probably or definitely related to MK-1966 or SD-101, was considered a DLT: 1. Grade (Gr) 4 non-hematologic toxicity; 2. Gr 4 hematologic toxicity lasting \>7 days, except thrombocytopenia: \*Gr 4 thrombocytopenia of any duration; \*Gr 3 thrombocytopenia if associated with bleeding; 3. Gr 3 non-hematologic toxicity lasting \>3 days despite optimal supportive care; 4. Any Gr 3 or Gr 4 non-hematologic laboratory abnormality, if: medical intervention is required OR abnormality leads to hospitalization OR abnormality persists for \>1 week; 5. Febrile neutropenia Gr 3 or Gr 4; 6. Any drug-related AE which caused participant to discontinue study drug during Cycle 1 7. Gr 5 toxicity; or 8. Delay in initiation of Cycle 2 for \>2 weeks due to study drug-related toxicity. The percentage of participants who experienced a DLT during Cycle 1 is presented. |
| Number of Participants With Adverse Events (AEs) | From first dose of study drug through 90 days after last dose of study drug (Up to approximately 22 weeks) | An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study drug or protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study drug, was also an AE. The number of participants who experienced as AE is presented. |
| Number of Participants Discontinuing Study Drug Due to AEs | From first dose of study drug up to last dose of study drug (Up to approximately 9 weeks) | The number of participants who discontinued study drug due to an AE is presented. |
Participant flow
Pre-assignment details
The study was terminated prior to completion of Part A enrollment and prior to initiation of Parts B or C enrollment. This results disclosure is for Part A only.
Participants by arm
| Arm | Count |
|---|---|
| MK-1966 70 mg+SD-101 1 mg Participants received a combination of MK-1966 70 mg intravenously (IV) (on Day 1 of each 3-week cycle for up to 8 cycles) and SD-101 1 mg intratumorally (IT) (on Days 1, 8 and 15 of Cycle 1, and then on Day 1 of up to 7 additional 3-week cycles) in Part A of the study. Participants were then to continue in one of two expansion cohorts (Part B or C) and were to receive up to 8 cycles of treatment on Day 1 of each 3-week cycle (approximately 24 weeks), but the study was terminated by the Sponsor prior to completion of Part A enrollment and prior to initiation of Parts B or C enrollment. | 3 |
| MK-1966 70 mg+SD-101 4 mg Participants received a combination of MK-1966 70 mg IV (on Day 1 of each 3-week cycle for up to 8 cycles) and SD-101 4 mg IT (on Days 1, 8 and 15 of Cycle 1, and then on Day 1 of up to 7 additional 3-week cycles) in Part A of the study. Participants were then to continue in one of two expansion cohorts (Part B or C) and were to receive up to 8 cycles of treatment on Day 1 of each 3-week cycle (approximately 24 weeks), but the study was terminated by the Sponsor prior to completion of Part A enrollment and prior to initiation of Parts B or C enrollment. | 3 |
| MK-1966 210 mg+SD-101 4 mg Participants received a combination of MK-1966 210 mg IV (on Day 1 of each 3-week cycle for up to 8 cycles) and SD-101 4 mg IT (on Days 1, 8 and 15 of Cycle 1, and then on Day 1 of up to 7 additional 3-week cycles) in Part A of the study. Participants were then to continue in one of two expansion cohorts (Part B or C) and were to receive up to 8 cycles of treatment on Day 1 of each 3-week cycle (approximately 24 weeks), but the study was terminated by the Sponsor prior to completion of Part A enrollment and prior to initiation of Parts B or C enrollment. | 6 |
| MK-1966 700 mg+SD-101 4 mg Participants received a combination of MK-1966 700 mg IV (on Day 1 of each 3-week cycle for up to 8 cycles) and SD-101 4 mg IT (on Days 1, 8 and 15 of Cycle 1, and then on Day 1 of up to 7 additional 3-week cycles) in Part A of the study. Participants were to continue in one of two expansion cohorts (Part B or C) and were to receive up to 8 cycles of treatment on Day 1 of each 3-week cycle (approximately 24 weeks), but the study was terminated by the Sponsor prior to completion of Part A enrollment and prior to initiation of Parts B or C enrollment. | 2 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 1 | 2 | 5 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 2 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | MK-1966 70 mg+SD-101 1 mg | Total | MK-1966 700 mg+SD-101 4 mg | MK-1966 210 mg+SD-101 4 mg | MK-1966 70 mg+SD-101 4 mg |
|---|---|---|---|---|---|
| Age, Continuous | 64.7 Years STANDARD_DEVIATION 1.5 | 61.9 Years STANDARD_DEVIATION 7 | 50.5 Years STANDARD_DEVIATION 2.1 | 63.7 Years STANDARD_DEVIATION 6.8 | 63.0 Years STANDARD_DEVIATION 6.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 14 Participants | 2 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 1 Participants | 3 Participants | 0 Participants |
| Sex: Female, Male Male | 0 Participants | 7 Participants | 1 Participants | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 2 / 3 | 5 / 6 | 0 / 2 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 6 / 6 | 2 / 2 |
| serious Total, serious adverse events | 1 / 3 | 1 / 3 | 3 / 6 | 1 / 2 |
Outcome results
Primary
Number of Participants Discontinuing Study Drug Due to AEs
The number of participants who discontinued study drug due to an AE is presented.
Time frame: From first dose of study drug up to last dose of study drug (Up to approximately 9 weeks)
Population: The safety analysis population consisted of all participants who received ≥1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-1966 70 mg+SD-101 1 mg | Number of Participants Discontinuing Study Drug Due to AEs | 0 Participants |
| MK-1966 70 mg+SD-101 4 mg | Number of Participants Discontinuing Study Drug Due to AEs | 0 Participants |
| MK-1966 210 mg+SD-101 4 mg | Number of Participants Discontinuing Study Drug Due to AEs | 1 Participants |
| MK-1966 700 mg+SD-101 4 mg | Number of Participants Discontinuing Study Drug Due to AEs | 0 Participants |
Primary
Number of Participants With Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of study drug or protocol-specified procedure, whether or not considered related to the study drug or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study drug, was also an AE. The number of participants who experienced as AE is presented.
Time frame: From first dose of study drug through 90 days after last dose of study drug (Up to approximately 22 weeks)
Population: The safety analysis population consisted of all participants who received ≥1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-1966 70 mg+SD-101 1 mg | Number of Participants With Adverse Events (AEs) | 3 Participants |
| MK-1966 70 mg+SD-101 4 mg | Number of Participants With Adverse Events (AEs) | 3 Participants |
| MK-1966 210 mg+SD-101 4 mg | Number of Participants With Adverse Events (AEs) | 6 Participants |
| MK-1966 700 mg+SD-101 4 mg | Number of Participants With Adverse Events (AEs) | 2 Participants |
Primary
Percentage of Participants With a Dose Limiting Toxicity (DLT)
The occurrence of any of the following toxicities during Cycle 1 (Days 1-21), if assessed by the Investigator to be possibly, probably or definitely related to MK-1966 or SD-101, was considered a DLT: 1. Grade (Gr) 4 non-hematologic toxicity; 2. Gr 4 hematologic toxicity lasting \>7 days, except thrombocytopenia: \*Gr 4 thrombocytopenia of any duration; \*Gr 3 thrombocytopenia if associated with bleeding; 3. Gr 3 non-hematologic toxicity lasting \>3 days despite optimal supportive care; 4. Any Gr 3 or Gr 4 non-hematologic laboratory abnormality, if: medical intervention is required OR abnormality leads to hospitalization OR abnormality persists for \>1 week; 5. Febrile neutropenia Gr 3 or Gr 4; 6. Any drug-related AE which caused participant to discontinue study drug during Cycle 1 7. Gr 5 toxicity; or 8. Delay in initiation of Cycle 2 for \>2 weeks due to study drug-related toxicity. The percentage of participants who experienced a DLT during Cycle 1 is presented.
Time frame: From time of first dose of study drug to the end of Cycle 1. Each cycle was 21 days. (Up to 21 days)
Population: The DLT evaluable population consisted of all participants who completed study drug in Cycle 1 or discontinued study drug during Cycle 1 due to a DLT.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-1966 70 mg+SD-101 1 mg | Percentage of Participants With a Dose Limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| MK-1966 70 mg+SD-101 4 mg | Percentage of Participants With a Dose Limiting Toxicity (DLT) | 0.0 Percentage of Participants |
| MK-1966 210 mg+SD-101 4 mg | Percentage of Participants With a Dose Limiting Toxicity (DLT) | 20.0 Percentage of Participants |
| MK-1966 700 mg+SD-101 4 mg | Percentage of Participants With a Dose Limiting Toxicity (DLT) | 0.0 Percentage of Participants |