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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04157517




Registration number
NCT04157517
Ethics application status
Date submitted
6/11/2019
Date registered
8/11/2019

Titles & IDs
Public title
A Study of Modakafusp Alfa (TAK-573) Given by Itself and Together With Pembrolizumab in Adults With Advanced or Metastatic Solid Tumors
Scientific title
An Open-Label, Dose-Escalation Phase 1b/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Modakafusp Alfa (TAK-573) as a Single Agent and in Combination With Pembrolizumab in Adult Patients With Advanced or Metastatic Solid Tumors
Secondary ID [1] 0 0
U1111-1238-9163
Secondary ID [2] 0 0
TAK-573-1001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Modakafusp Alfa
Treatment: Drugs - Pembrolizumab

Experimental: Phase 1b SA Dose Escalation - Modakafusp alfa 0.1 to 6 milligram per kilogram (mg/kg), infusion, intravenously, once on Day 1 of each 21-days treatment cycle for up to 1 year.

Experimental: Phase 2 Safety Lead-in Dose Expansion: Modakafusp Alfa + Pembrolizumab - Melanoma with primary resistance to prior anti-PD1, acquired resistance to prior anti-PD1 or naïve to anti-PD1.

Modakafusp alfa, infusion, intravenously, once on Day 1 of each 21-days treatment cycle and pembrolizumab 400 mg infusion, intravenously, once every 6 weeks for up to 2 years. The starting dose of modakafusp alfa for dose expansion safety lead-in phase will be the RP2D determined in the previous Phase 1b dose escalation phase.

Experimental: Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma With Primary Resistance) - Melanoma With Primary Resistance to prior anti-PD1. Modakafusp alfa, infusion, intravenously, once on Day 1 of each 21-days treatment cycle and pembrolizumab 400 mg infusion, intravenously, once every 6 weeks for up to 2 years, in participants with unresectable/metastatic cutaneous melanoma with primary resistance to no more than 2 prior lines of anti-PD1 containing treatments in the metastatic setting. The dose of modakafusp alfa for dose expansion phase will be the modakafusp alfa RP2D in combination with pembrolizumab determined in the previous Phase 2 dose expansion safety-lead in phase.

Experimental: Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma With Acquired Resistance) - Melanoma With Acquired Resistance to prior anti-PD1. Modakafusp alfa, infusion, intravenously, once on Day 1 of each 21-days treatment cycle and pembrolizumab 400 mg infusion, intravenously, once every 6 weeks for up to 2 years, in participants with unresectable/metastatic cutaneous melanoma with acquired resistance to no more than 2 prior lines of anti-PD1 containing treatments in the metastatic setting. The dose of modakafusp alfa for dose expansion phase will be the modakafusp alfa RP2D in combination with pembrolizumab determined in the previous Phase 2 dose expansion safety lead-in phase.

Experimental: Phase 2 Dose Expansion: Modakafusp Alfa + Pembrolizumab (Melanoma naïve to anti-PD1) - Modakafusp alfa, infusion, intravenously, once on Day 1 of each 21-days treatment cycle and pembrolizumab 400 mg infusion, intravenously, once every 6 weeks for up to 2 years, in participants with unresectable/metastatic cutaneous melanoma naive to prior line of anti-PD1 containing treatments in the metastatic setting. The dose of modakafusp alfa for dose expansion phase will be the modakafusp alfa RP2D in combination with pembrolizumab determined in the previous Phase 2 dose expansion safety lead-in phase.


Treatment: Drugs: Modakafusp Alfa
Modakafusp alfa intravenous infusion.

Treatment: Drugs: Pembrolizumab
Pembrolizumab intravenous infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b and Phase 2 Safety Lead-in: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Assessment method [1] 0 0
Adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment. A TEAE was any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug.
Timepoint [1] 0 0
From signing of the informed consent form (ICF) through 30 days after last dose of study drug or the start of subsequent anticancer therapy, whichever occurred first (up to 1 year 1 month for Phase 1b and 2 years 1 month for Phase 2)
Primary outcome [2] 0 0
Phase 1b and Phase 2 Safety Lead-in: Number of Participants With Grade 3 or Higher TEAEs
Assessment method [2] 0 0
TEAEs Grades were evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0. (NCI CTCAE v5), where Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL). Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Timepoint [2] 0 0
From signing of the ICF through 30 days after last dose of study drug or the start of subsequent anticancer therapy, whichever occurred first (up to 1 year 1 month for Phase 1b and 2 years 1 month for Phase 2)
Primary outcome [3] 0 0
Phase 1b and Phase 2 Safety Lead-in: Number of Participants With Dose Limiting Toxicities (DLTs)
Assessment method [3] 0 0
A DLT was defined as any of the following AEs that occurred in the escalation phase or in the combination safety lead-in phase during Cycle 1 unless they were considered by the investigator to be clearly unrelated to therapy with modakafusp alfa according to NCI CTCAE version 5.0. Any Grade 5 TEAE. Febrile neutropenia: Grade \>=3 or 4 neutropenia. Grade 4 thrombocytopenia. Grade \>=3 thrombocytopenia. Any Grade 3 immune-related AEs such as pericarditis, pneumonitis, cardiotoxicity, hepatitis, or neurotoxicity. Delay in the initiation of Cycle 2 by more than 14 days from the calculated start date due to a lack of adequate recovery of treatment-related hematological or nonhematologic toxicities. Any Grade \>=3 nonhematologic toxicity with some exception. Any Grade 2 nonhematologic toxicity that was considered by the investigator to be related to study drug and dose-limiting.
Timepoint [3] 0 0
Cycle 1 (Cycle length is equal to [=] 21 days)
Primary outcome [4] 0 0
Phase 1b and Phase 2 Safety Lead-in: Number of Participants Reporting One or More Serious Adverse Event (SAEs)
Assessment method [4] 0 0
SAE was defined as any untoward medical occurrence that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of an existing hospitalization; resulted in persistent or significant disability or incapacity; was a congenital anomaly/birth defect; was a medically important event that might not result in death, be immediately life-threatening, or required hospitalization, but might be considered serious when, on the basis of appropriate medical judgment, it might jeopardize the participant, required medical or surgical intervention to prevent one of the outcomes listed above, or involves suspected transmission via a medicinal product of an infectious agent.
Timepoint [4] 0 0
From signing of the ICF through 30 days after last dose of study drug even if the participants start non-protocol systemic therapy (up to 1 year 1 month for Phase 1b and 2 years 1 month for Phase 2)
Primary outcome [5] 0 0
Phase 1b and Phase 2 Safety Lead-in: Number of Participants With One or More TEAEs Leading to Dose Modifications and Treatment Discontinuations
Assessment method [5] 0 0
TEAE was defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug.
Timepoint [5] 0 0
From signing of the ICF through 30 days after last dose of study drug or the start of subsequent anticancer therapy, whichever occurred first (up to 1 year 1 month for Phase 1b and 2 years 1 month for Phase 2)
Primary outcome [6] 0 0
Phase 2 Expansion: Overall Response Rate (ORR) Based on RECIST v1.1
Assessment method [6] 0 0
ORR was defined as the percentage of participants who achieved complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR: At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Timepoint [6] 0 0
From the first dose of study drug up to end of treatment or end of study (up to 2 years)
Secondary outcome [1] 0 0
Phase 1b: Maximum Tolerated Dose (MTD) of Modakafusp Alfa
Assessment method [1] 0 0
The MTD was selected as the highest dose which has maximum probability of being in targeted toxicity interval.
Timepoint [1] 0 0
Cycle 1 (Cycle length = 21 days)
Secondary outcome [2] 0 0
Phase 1b and Phase 2 Safety Lead-in: Recommended Phase 2 Dose (RP2D) for Single Agent (SA) Modakafusp Alfa in Phase 1b and in Combination With Pembrolizumab in Phase 2 Safety Lead-in
Assessment method [2] 0 0
The RP2D of modakafusp alfa as a single agent or in combination with pembrolizumab was determined based on safety (including DLTs), pharmacokinetic and clinical data. DLT was graded according to CTCAE v5.0.
Timepoint [2] 0 0
Cycle 1 (Cycle length = 21 days)
Secondary outcome [3] 0 0
Phase 2 Expansion: Number of Participants Reporting One or More TEAEs
Assessment method [3] 0 0
AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence did not necessarily have a causal relationship with this treatment. A TEAE was any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug.
Timepoint [3] 0 0
From signing of the ICF through 30 days after last dose of study drug or the start of subsequent anticancer therapy, whichever occurred first (up to 2 years 1 month)
Secondary outcome [4] 0 0
Phase 2 Expansion: Number of Participants With Grade 3 or Higher TEAEs
Assessment method [4] 0 0
TEAEs Grades were evaluated as per the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0. (NCI CTCAE v5), where Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL). Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.
Timepoint [4] 0 0
From signing of the ICF through 30 days after last dose of study drug or the start of subsequent anticancer therapy, whichever occurred first (up to 2 years 1 month)
Secondary outcome [5] 0 0
Phase 2 Expansion: Number of Participants Reporting One or More SAEs
Assessment method [5] 0 0
SAE was defined as any untoward medical occurrence that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of an existing hospitalization; resulted in persistent or significant disability or incapacity; was a congenital anomaly/birth defect; was a medically important event that might not result in death, be immediately life-threatening, or required hospitalization, but might be considered serious when, on the basis of appropriate medical judgment, it might jeopardize the participant, required medical or surgical intervention to prevent one of the outcomes listed above, or involves suspected transmission via a medicinal product of an infectious agent.
Timepoint [5] 0 0
From signing of the ICF through 30 days after last dose of study drug even if the participants start non-protocol systemic therapy (up to 2 years 1 month)
Secondary outcome [6] 0 0
Phase 2 Expansion: Number of Participants With One or More TEAEs Leading to Dose Modifications and Treatment Discontinuations
Assessment method [6] 0 0
TEAE was defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last administration of study drug.
Timepoint [6] 0 0
From signing of the ICF through 30 days after last dose of study drug or the start of subsequent anticancer therapy, whichever occurred first (up to 2 years 1 month)
Secondary outcome [7] 0 0
Phase 1b and Phase 2 Safety Lead-in: Maximum Observed Serum Concentration (Cmax) for Modakafusp Alfa
Assessment method [7] 0 0
Cmax for modakafusp alfa was reported.
Timepoint [7] 0 0
Phase 1b, Cycles 1 and 2 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion; Phase 2, Safety lead-in, Cycles 1 and 3 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion (each cycle length=21 days)
Secondary outcome [8] 0 0
Phase 1b and Phase 2 Safety Lead-in: Time to Reach the Cmax (Tmax) for Modakafusp Alfa
Assessment method [8] 0 0
Tmax for modakafusp alfa was reported.
Timepoint [8] 0 0
Phase 1b, Cycles 1 and 2 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion; Phase 2, Safety lead-in, Cycles 1 and 3 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion (each cycle length=21 days)
Secondary outcome [9] 0 0
Phase 1b and Phase 2 Safety Lead-in: Area Under the Plasma Concentration-time Curve From Time 0 to Last Measurable Concentration (AUClast) for Modakafusp Alfa
Assessment method [9] 0 0
AUClast for modakafusp alfa was reported.
Timepoint [9] 0 0
Phase 1b, Cycles 1 and 2 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion; Phase 2, Safety lead-in, Cycles 1 and 3 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion (each cycle length=21 days)
Secondary outcome [10] 0 0
Phase 1b and Phase 2 Safety Lead-in: Area Under the Serum Concentration-time Curve From Time 0 to Infinity (AUCinf) for Modakafusp Alfa
Assessment method [10] 0 0
AUCinf of modakafusp alfa was reported.
Timepoint [10] 0 0
Phase 1b, Cycles 1 and 2 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion; Phase 2, Safety lead-in, Cycles 1 and 3 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion (each cycle length=21 days)
Secondary outcome [11] 0 0
Phase 1b and Phase 2 Safety Lead-in: Terminal Disposition Phase Half-life (t1/2z) for Modakafusp Alfa
Assessment method [11] 0 0
T1/2z of modakafusp alfa was reported.
Timepoint [11] 0 0
Phase 1b, Cycles 1 and 2 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion; Phase 2, Safety lead-in, Cycles 1 and 3 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion (each cycle length=21 days)
Secondary outcome [12] 0 0
Phase 1b and Phase 2 Safety Lead-in: Total Clearance (CL) After Intravenous Administration for Modakafusp Alfa
Assessment method [12] 0 0
CL was total clearance of the drug from the serum. CL of modakafusp alfa was reported.
Timepoint [12] 0 0
Phase 1b, Cycles 1 and 2 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion; Phase 2, Safety lead-in, Cycles 1 and 3 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion (each cycle length=21 days)
Secondary outcome [13] 0 0
Phase 1b and Phase 2 Safety Lead-in: Volume of Distribution at Steady State (Vss) for Modakafusp Alfa
Assessment method [13] 0 0
Vss of modakafusp alfa was reported.
Timepoint [13] 0 0
Phase 1b, Cycles 1 and 2 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion; Phase 2, Safety lead-in, Cycles 1 and 3 Day 1: Pre-infusion and at multiple timepoints (up to 72 hours) post-infusion (each cycle length=21 days)
Secondary outcome [14] 0 0
Phase 1b and Phase 2 Safety Lead-in: ORR Based on RECIST v1.1
Assessment method [14] 0 0
ORR was defined as the percentage of participants who achieved CR or PR as per RECIST version 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Timepoint [14] 0 0
From the first dose of study drug up to end of treatment or end of study (up to 1 year for Phase 1b and 2 years for Phase 2)
Secondary outcome [15] 0 0
Phase 1b and Phase 2: Disease Control Rate (DCR) Based on RECIST v1.1
Assessment method [15] 0 0
DCR was defined as the percentage of participants who achieved CR, PR, or stable disease (SD) (determined by the investigator) as per RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression (PD), taking as reference the smallest sum diameters while on study.
Timepoint [15] 0 0
From the first dose of study drug up to end of treatment or end of study (up to 1 year for Phase 1b and 2 years for Phase 2)
Secondary outcome [16] 0 0
Phase 1b and Phase 2: Duration of Response (DOR) Based on RECIST v1.1
Assessment method [16] 0 0
DOR was defined as the time from the first documentation of a response (CR or PR) until PD or death, whichever occurred first as per RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Timepoint [16] 0 0
From the date of first documentation of a CR or PR until PD or death, whichever occurred first (up to end of treatment or end of study [1 year for Phase 1b and 2 years for Phase 2])
Secondary outcome [17] 0 0
Phase 1b and Phase 2: Time to Progression (TTP) Based on RECIST v1.1
Assessment method [17] 0 0
TTP was defined as the time from the date of the first dose of study drug to the date of the first documentation of PD according to RECIST v1.1. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Timepoint [17] 0 0
From the date of the first dose of study drug to the date of the first documentation of PD (up to end of treatment or end of study [1 year for Phase 1b and 2 years for Phase 2])
Secondary outcome [18] 0 0
Phase 1b and Phase 2: Progression Free Survival (PFS) Based on RECIST v1.1
Assessment method [18] 0 0
PFS was defined as the time from the date of the first dose of study drug to the date of first documentation of PD according to RECIST v.1.1, or death due to any cause, whichever occurred first. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Timepoint [18] 0 0
From the date of the first dose of study drug to the date of first documentation of PD or death, whichever occurred first (up to end of treatment or end of study [1 year for Phase 1b and 2 years for Phase 2])
Secondary outcome [19] 0 0
Phase 1b and Phase 2: Overall Survival (OS) Based on RECIST v1.1
Assessment method [19] 0 0
OS was defined as the time from the date of first dose of study drug to the date of death due to any cause.
Timepoint [19] 0 0
From the date of first dose of study drug to the date of death due to any cause (up to end of treatment or end of study [1 year for Phase 1b and 2 years for Phase 2])
Secondary outcome [20] 0 0
Phase 2 Expansion: ORR Based on Based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST)
Assessment method [20] 0 0
ORR was defined as the percentage of participants whose BOR was immune CR (iCR) or immune PR (iPR), according to iRECIST as per investigator assessment. iCR: immune complete response achieved with disappearance of all target lesions immune confirmed progressive disease (iCPD). (iCPD): immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. iSD: immune stable disease in the absence of iCR or immune PD (iPD). iUPD: immune unconfirmed progressive disease (iUPD) when iCPD is unconfirmed NE: not evaluable.
Timepoint [20] 0 0
From date of first dose of study drug until confirmed iCR or iPR (up to end of treatment or end of study [up to 2 years])
Secondary outcome [21] 0 0
Phase 2 Expansion: DCR Based on iRECIST
Assessment method [21] 0 0
DCR was defined as percentage of participants who have achieved the best response of iCR, iPR, iSD based on iRECIST as per investigator assessment. iCR: achieved with disappearance of all target lesions, iPR: achieved with disappearance of partial target lesions. iSD: in the absence of iCR or iCPD. iUPD: when iPD is unconfirmed NE: not evaluable.
Timepoint [21] 0 0
From date of first dose of study drug until confirmed iCR or iPR (up to end of treatment or end of study [up to 2 years])
Secondary outcome [22] 0 0
Phase 2 Expansion: DOR Based on iRECIST
Assessment method [22] 0 0
DOR was defined as time from date of first observation of response (iPR or iCR) to date of the first observation of progression (iCPD) based on iRECIST as per investigator assessment, or date of death, whatever the cause. iCR: immune complete response achieved with disappearance of all target lesions iCPD: immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Timepoint [22] 0 0
From first documented confirmed iCR or iPR until first documentation of iCPD or death (up to end of treatment or end of study [up to 2 years])
Secondary outcome [23] 0 0
Phase 2 Expansion: TTP Based on iRECIST
Assessment method [23] 0 0
TTP was defined as the time from the date of the first dose of study drug to the date of the first documentation of iCPD based on iRECIST as per investigator assessment. iCPD: immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Timepoint [23] 0 0
From the date of the first dose of study drug to the date of the first documentation of iCPD (up to end of treatment or end of study [up to 2 years])
Secondary outcome [24] 0 0
Phase 2 Expansion: PFS Based on iRECIST
Assessment method [24] 0 0
PFS was defined as the time from the first dose date to the date of iCPD or date of death (whichever occurred first) based on iRECIST as per investigator assessment. iCPD was defined as immune confirmed progressive disease when there is either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Timepoint [24] 0 0
From first dose of study drug until confirmed iCPD or death (up to end of treatment or end of study [up to 2 years])
Secondary outcome [25] 0 0
Phase 1b and Phase 2: Number of Participants With Positive Anti-Modakafusp Alfa Antibodies (ADA) Status
Assessment method [25] 0 0
ADA samples scoring equal to or above the cut-point (titer of 75) were defined as ADA positive.
Timepoint [25] 0 0
Baseline up to end of treatment or end of study (up to 1 year for Phase 1b and 2 years for Phase 2)
Secondary outcome [26] 0 0
Phase 1b and Phase 2: Titer of Anti-Modakafusp Alfa Antibodies (ADA)
Assessment method [26] 0 0
ADA titers were assessed by confirmatory assay.
Timepoint [26] 0 0
Baseline up to end of treatment or end of study (up to 1 year for Phase 1b and 2 years for Phase 2)

Eligibility
Key inclusion criteria
1. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
2. For both the dose escalation and expansion cohort phases of the study, eligible participants must have histologically confirmed advanced (locoregionally recurrent, not amenable to curative therapy) or metastatic solid tumors.
3. Measurable disease per RECIST v1.1. At least 1 target lesion amenable for biopsy is required for enrollment in phase 1b. A minimum of 1 target lesion for response assessment is required for enrollment in phase 2. A separate lesion amenable for biopsy is required for enrollment in phase 2 for cohorts I and II post futility analysis and for all participants (safety lead-in and expansion) with subgroup III melanoma.
4. Phase 1b Dose Escalation: Participants with histologically confirmed advanced locally (locoregionally recurrent, not amenable to curative therapy) or metastatic solid tumors.

Phase 2 Dose Expansion:

The combination cohorts, including participants in the safety-lead phase, will enroll participants with unresectable/metastatic melanoma in the following subgroups:

I. Unresectable/metastatic histologically confirmed cutaneous melanoma with primary resistance to no more than 2 prior lines of anti-PD1 containing treatments in the metastatic setting.

II. Unresectable/metastatic histologically confirmed cutaneous melanoma with acquired resistance to no more than 2 prior lines of anti-PD1 containing treatments in the metastatic setting.

III. Unresectable/metastatic histologically confirmed cutaneous melanoma naive to prior anti-PD1 containing treatments in the metastatic setting.

* Participants with BRAF V600E mutant melanoma may have received prior BRAF inhibitor therapy.
* For the expansion cohorts I and II, there is no limitation of total number of prior line(s) of therapy, but the number of prior line(s) containing anti-PD1 must be =2 in the metastatic setting.
* For the expansion cohort III, participants who received an anti-PD-1 treatment in the adjuvant setting must have completed that treatment at least 6 months prior to enrollment and must not have progressed on the anti-PD1 adjuvant treatment.
* Primary resistance is defined as a best response of PD or SD less than (<) 6 months to an anti-PD1 alone or in combination with other agents (that is, CTLA4) in the initial anti-PD1 containing treatment.
* Acquired resistance is defined as a progression following a best response of CR, PR or SD>6 months to a prior anti-PD1 alone or in combination with other agents (that is, CTLA4).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Persistent toxicity from previous treatments that has not resolved to less than or equal to (<=) CTCAE version 5.0 Grade 1 prior to administration of modakafusp alfa, except for alopecia, Grade 2 neuropathy, and Grade 2 asthenia/fatigue, or autoimmune endocrinopathies with stable replacement therapy.
2. History of any of the following <=6 months before first dose modakafusp alfa: New York Heart Association (NYHA) Grade III or IV congestive heart failure, unstable angina, myocardial infarction, unstable symptomatic ischemic heart disease, any ongoing symptomatic cardiac arrhythmias of Grade >2, pulmonary embolism, or symptomatic cerebrovascular events, or any other serious cardiac condition (example, symptomatic pericardial effusion or restrictive cardiomyopathy). Chronic, stable atrial fibrillation on stable anticoagulant therapy, including low molecular-weight heparin, is allowed.
3. Baseline QT interval with Fridericia's correction (QTcF) greater than (>) 480 millisecond (msec) (Grade >=2), history of congenital long QT syndrome, or torsades de pointes.
4. Patients with acral lentiginous melanoma are excluded in phase 2 except for the safety lead-in phase.
5. Ongoing or active infection.
6. Known history of human immunodeficiency virus (HIV) infection or any other relevant congenital or acquired immunodeficiency. Testing during screening period is required only if indicated by specific local regulations or investigator's criteria.
7. Known hepatitis B (HBV) surface antigen seropositive or detectable hepatitis C infection viral load. Note: Participants with a positive HBV core antibody can be enrolled but must have an undetectable hepatitis B viral load.
8. Autoimmune disease requiring systemic immunosuppressive therapy. Participants with immune mediated endocrine deficiency from previous therapy with stable hormone replacement are exceptions.

Study design
Purpose of the study
Other
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/12/2023
Sample size
Target
Accrual to date
Final
45
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [2] 0 0
Ballarat Regional Integrated Cancer Center - Ballarat
Recruitment postcode(s) [1] 0 0
5011 - Woodville South
Recruitment postcode(s) [2] 0 0
3350 - Ballarat
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
New Hampshire
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
South Dakota
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Utah
Country [12] 0 0
United States of America
State/province [12] 0 0
West Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Takeda
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
Takeda
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol
Statistical analysis plan



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04157517