Study of ADCT-301 in Patients With Selected Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT03621982
• Recruitment Status: Terminated
• First Posted: August 9, 2018
• Last Update Posted: March 17, 2023
• Sponsor: ADC Therapeutics S.A.
• Information provided by (Responsible Party): ADC Therapeutics S.A.

Study Description

Brief Summary:

This study evaluates ADCT-301 in patients with Selected Advanced Solid Tumors. Patients will participate in a Treatment Period with 3-week cycles and a Follow-up Period every 12 weeks for up to 1 year after treatment discontinuation.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors With Literature Evidence of CD25(+) Treg Content; Head and Neck Cancer Squamous Cell Carcinoma; Non-small Cell Lung Cancer; Gastric Cancer; Esophageal Cancer; Pancreas Cancer; Bladder Cancer; Renal Cell Carcinoma; Melanoma; Triple-negative Breast Cancer; Ovarian Cancer; Colo-rectal Cancer; Fallopian Tube Cancer	Drug: ADCT-301; Biological: Pembrolizumab	Phase 1

Detailed Description:

This is a Phase 1b, multi-center, open-label study with a dose-escalation part and a dose expansion part.

The duration of the study participation for each patient is defined as the time from the date of signed written informed consent to the completion of the follow-up period, withdrawal of consent, loss to follow-up, or death, whichever occurs first.

The study will include a Screening Period (of up to 21 days), a Treatment Period (with cycles of 3 weeks for a Q3W dosing regimen), and a Follow-up Period (approximately every 12 week visits) for up to 1 year after treatment discontinuation

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 78 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Camidanlumab Tesirine (ADCT-301) as Monotherapy or in Combination in Patients With Selected Advanced Solid Tumors
• Actual Study Start Date: November 9, 2018
• Actual Primary Completion Date: December 8, 2022
• Actual Study Completion Date: December 8, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1: Dose Escalation, ADCT-301 Monotherapy; In Part 1 (dose escalation) patients will receive escalating doses of ADCT-301 as monotherapy.	Drug: ADCT-301; intravenous infusion; Other Name: Camidanlumab tesirine
Experimental: Part 1: Dose Escalation, ADCT-301 Combination Therapy; In Part 1 (dose escalation) patients will receive escalating doses of ADCT-301 in combination with pembrolizamab as combination therapy.	Drug: ADCT-301; intravenous infusion; Other Name: Camidanlumab tesirine; Biological: Pembrolizumab; intravenous infusion; Other Name: Keytruda
Experimental: Part 2: Dose expansion, ADCT-301 Combination Therapy; In Part 2 (dose expansion), patients will receive ADCT-301 in combination with pembrolizamab as combination therapy at the dose identified in Part 1 (dose escalation). Patients will be split into two groups: Group 1: One of the indications identified in Part 1, for which at least 1 response (PR [partial response] or CR [complete response]) was seen. Group 2: A basket group of patients with advanced/metastatic solid tumors and microsatellite instability/deficient MisMatch Repair (MSI-H/dMMR) status, who have received prior regimen containing a PD-1/PD-L1 inhibitor, for which the best response was CR, PR, or SD (stable disease) ≥4 months, and then progressed while continuing on the PD-1/PD-L1 inhibitor-based regimen.	Drug: ADCT-301; intravenous infusion; Other Name: Camidanlumab tesirine; Biological: Pembrolizumab; intravenous infusion; Other Name: Keytruda

Outcome Measures

Primary Outcome Measures :

1. Part 1 Monotherapy: Number of Patients Who Experience a Treatment-emergent Adverse Event (TEAE) [ Time Frame: Up to 3 years ]
   An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an AE that occurs or worsens in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy, whichever is earlier.
2. Part 1 Combination Therapy: Number of Patients Who Experience a Treatment-emergent Adverse Event (TEAE) [ Time Frame: Up to 3 years ]
   An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an AE that occurs or worsens in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy, whichever is earlier.
3. Part 2 Combination Therapy: Number of Patients Who Experience a Treatment-emergent Adverse Event (TEAE) [ Time Frame: Up to 3 years ]
   An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an AE that occurs or worsens in the period extending from the first dose of study drug to 30 days after the last dose of study drug in this study or start of a new anticancer therapy, whichever is earlier.
4. Part 1 Monotherapy: Number of Patients Who Experience a Treatment-emergent Adverse Event (TEAE) of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Up to 3 years ]
   AEs will be graded according to CTCAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5, where 1 is asymptomatic or mild symptoms and 5 is death related to an AE.
5. Part 1 Combination Therapy: Number of Patients Who Experience a Treatment-emergent Adverse Event (TEAE) of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Up to 3 years ]
   AEs will be graded according to CTCAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5, where 1 is asymptomatic or mild symptoms and 5 is death related to an AE.
6. Part 2 Combination Therapy: Number of Patients Who Experience a Treatment-emergent Adverse Event (TEAE) of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Up to 3 years ]
   AEs will be graded according to CTCAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5, where 1 is asymptomatic or mild symptoms and 5 is death related to an AE.
7. Part 1 Monotherapy: Number of Patients Who Experience a Serious Adverse Event (SAE) [ Time Frame: Up to 3 years ]
   A SAE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization of prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance is not considered an SAE), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the patient or may require medical or surgical intervention to prevent any of the outcomes listed above.
8. Part 1 Combination Therapy: Number of Patients Who Experience a Serious Adverse Event (SAE) [ Time Frame: Up to 3 years ]
   A SAE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization of prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance is not considered an SAE), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the patient or may require medical or surgical intervention to prevent any of the outcomes listed above.
9. Part 2 Combination Therapy: Number of Patients Who Experience a Serious Adverse Event (SAE) [ Time Frame: Up to 3 years ]
   A SAE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization of prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance is not considered an SAE), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the patient or may require medical or surgical intervention to prevent any of the outcomes listed above.
10. Part 1 Monotherapy: Number of Patients with a Serious Adverse Event (SAE) of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Up to 3 years ]
    AEs will be graded according to CTCAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5, where 1 is asymptomatic or mild symptoms and 5 is death related to an AE.
11. Part 1 Combination Therapy: Number of Patients with a Serious Adverse Event (SAE) of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Up to 3 years ]
    AEs will be graded according to CTCAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5, where 1 is asymptomatic or mild symptoms and 5 is death related to an AE.
12. Part 2 Combination Therapy: Number of Patients with a Serious Adverse Event (SAE) of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Up to 3 years ]
    AEs will be graded according to CTCAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5, where 1 is asymptomatic or mild symptoms and 5 is death related to an AE.
13. Part 1 Monotherapy: Number of Patients who Experience a Clinically Significant Change from Baseline in Laboratory Values [ Time Frame: Baseline to up to 3 years ]
14. Part 1 Combination Therapy: Number of Patients who Experience a Clinically Significant Change from Baseline in Laboratory Values [ Time Frame: Baseline to up to 3 years ]
15. Part 2 Combination Therapy: Number of Patients who Experience a Clinically Significant Change from Baseline in Laboratory Values [ Time Frame: Baseline to up to 3 years ]
16. Part 1 Monotherapy: Number of Patients who Experience a Clinically Significant Change from Baseline in Vital Signs [ Time Frame: Baseline to up to 3 years ]
17. Part 1 Combination Therapy: Number of Patients who Experience a Clinically Significant Change from Baseline in Vital Signs [ Time Frame: Baseline to up to 3 years ]
18. Part 2 Combination Therapy: Number of Patients who Experience a Clinically Significant Change from Baseline in Vital Signs [ Time Frame: Baseline to up to 3 years ]
19. Part 1 Monotherapy: Number of Patients who Experience a Clinically Significant Change from Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Baseline to up to 3 years ]
20. Part 1 Combination Therapy: Number of Patients who Experience a Clinically Significant Change from Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Baseline to up to 3 years ]
21. Part 2 Combination Therapy: Number of Patients who Experience a Clinically Significant Change from Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Baseline to up to 3 years ]
22. Part 1 Monotherapy: Number of Patients who Experience a Clinically Significant Change from Baseline in 12-lead Electrocardiograms (ECGs) [ Time Frame: Baseline to up to 3 years ]
23. Part 1 Combination Therapy: Number of Patients who Experience a Clinically Significant Change from Baseline in 12-lead Electrocardiograms (ECGs) [ Time Frame: Baseline to up to 3 years ]
24. Part 2 Combination Therapy: Number of Patients who Experience a Clinically Significant Change from Baseline in 12-lead Electrocardiograms (ECGs) [ Time Frame: Baseline to up to 3 years ]
25. Part 1 Monotherapy: Number of Patients who Experience a Dose Interruption [ Time Frame: Up to 3 years ]
26. Part 1 Combination Therapy: Number of Patients who Experience a Dose Interruption [ Time Frame: Up to 3 years ]
27. Part 2 Combination Therapy: Number of Patients who Experience a Dose Interruption [ Time Frame: Up to 3 years ]
28. Part 1 Monotherapy: Number of Patients who Experience a Dose Reduction [ Time Frame: Up to 3 years ]
29. Part 1 Combination Therapy: Number of Patients who Experience a Dose Reduction [ Time Frame: Up to 3 years ]
30. Part 2 Combination Therapy: Number of Patients who Experience a Dose Reduction [ Time Frame: Up to 3 years ]
31. Part 1 Monotherapy: Number of Patients who Experience a Dose Limiting Toxicity (DLT) [ Time Frame: Day 1 to Day 21 ]
32. Part 1 Combination Therapy: Number of Patients who Experience a Dose Limiting Toxicity (DLT) [ Time Frame: Day 1 to Day 21 ]

Secondary Outcome Measures :

1. Part 1 Monotherapy: Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]
   ORR assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
2. Part 1 Combination Therapy: Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]
   ORR assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
3. Part 2 Combination Therapy: Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]
   ORR assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
4. Part 1 Monotherapy: Duration of Response (DOR) [ Time Frame: Up to 3 years ]
   DOR is defined as the time from the first documentation of tumor response to disease progression as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
5. Part 1 Combination Therapy: Duration of Response (DOR) [ Time Frame: Up to 3 years ]
   DOR is defined as the time from the first documentation of tumor response to disease progression as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
6. Part 2 Combination Therapy: Duration of Response (DOR) [ Time Frame: Up to 3 years ]
   DOR is defined as the time from the first documentation of tumor response to disease progression as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
7. Part 1 Monotherapy: Progression-free survival (PFS) [ Time Frame: Up to 3 years ]
   PFS is defined as the time between start of treatment and the first documentation of recurrence or progression as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
8. Part 1 Combination Therapy: Progression-free survival (PFS) [ Time Frame: Up to 3 years ]
   PFS is defined as the time between start of treatment and the first documentation of recurrence or progression as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
9. Part 2 Combination Therapy: Progression-free survival (PFS) [ Time Frame: Up to 3 years ]
   PFS is defined as the time between start of treatment and the first documentation of recurrence or progression as per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
10. Part 1 Monotherapy: Overall Survival (OS) [ Time Frame: Up to 3 years ]
    OS is defined as the time between the start of treatment and death from any cause.
11. Part 1 Combination Therapy: Overall Survival (OS) [ Time Frame: Up to 3 years ]
    OS is defined as the time between the start of treatment and death from any cause.
12. Part 2 Combination Therapy: Overall Survival (OS) [ Time Frame: Up to 3 years ]
    OS is defined as the time between the start of treatment and death from any cause.
13. Part 1 Monotherapy: Maximum Concentration (Cmax) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
14. Part 1 Combination Therapy: Maximum Concentration (Cmax) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
15. Part 2 Combination Therapy: Maximum Concentration (Cmax) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
16. Part 1 Monotherapy: Time to Maximum Concentration (Tmax) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
17. Part 1 Combination Therapy: Time to Maximum Concentration (Tmax) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
18. Part 2 Combination Therapy: Time to Maximum Concentration (Tmax) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
19. Part 1 Monotherapy: Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUC0-last) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
20. Part 1 Combination Therapy: Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUC0-last) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
21. Part 2 Combination Therapy: Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUC0-last) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
22. Part 1 Monotherapy: Area Under the Concentration-time Curve from Time Zero to Infinity (AUC0-∞) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
23. Part 1 Combination Therapy: Area Under the Concentration-time Curve from Time Zero to Infinity (AUC0-∞) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
24. Part 2 Combination Therapy: Area Under the Concentration-time Curve from Time Zero to Infinity (AUC0-∞) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
25. Part 1 Monotherapy: Area Under the Concentration-time Curve from Time Zero to the End of the Dosing Interval (AUC0-τ) Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
26. Part 1 Combination Therapy: Area Under the Concentration-time Curve from Time Zero to the End of the Dosing Interval (AUC0-τ) Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
27. Part 2 Combination Therapy: Area Under the Concentration-time Curve from Time Zero to the End of the Dosing Interval (AUC0-τ) Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
28. Part 1 Monotherapy: Accumulation Index (AI) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
29. Part 1 Combination Therapy: Accumulation Index (AI) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
30. Part 2 Combination Therapy: Accumulation Index (AI) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
31. Part 1 Monotherapy: Clearance (CL) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
32. Part 1 Combination Therapy: Clearance (CL) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
33. Part 2 Combination Therapy: Clearance (CL) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
34. Part 1 Monotherapy: Volume of Distribution (Vd) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
35. Part 1 Combination Therapy: Volume of Distribution (Vd) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
36. Part 2 Combination Therapy: Volume of Distribution (Vd) of Camidanlumab Tesirine in Serum [ Time Frame: Up to 3 years ]
    Total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199 will be measured.
37. Part 1 Monotherapy: Number of Patients with Confirmed Positive Anti-drug Antibody (ADA) Responses [ Time Frame: Up to 3 years ]
    ADA titers if applicable, neutralizing activity to camidanlumab tesirine after treatment with camidanlumab tesirine.
38. Part 1 Combination Therapy: Number of Patients with Confirmed Positive Anti-drug Antibody (ADA) Responses [ Time Frame: Up to 3 years ]
    ADA titers if applicable, neutralizing activity to camidanlumab tesirine after treatment with camidanlumab tesirine.
39. Part 2 Combination Therapy: Number of Patients with Confirmed Positive Anti-drug Antibody (ADA) Responses [ Time Frame: Up to 3 years ]
    ADA titers if applicable, neutralizing activity to camidanlumab tesirine after treatment with camidanlumab tesirine.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Written informed consent must be obtained prior to any procedures.
2. Male or female patient aged 18 years or older.

3. Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic at time of Screening:

   Part 1 Dose escalation camidanlumab tesirine as monotherapy:

   Selected advanced solid tumors: colorectal, head and neck, NSCLC, gastric and esophageal cancers, pancreas, bladder, renal cell carcinoma, melanoma, TNBC, and ovarian/fallopian tube cancers

   Part 1 Dose-escalation camidanlumab tesirine in combination with pembrolizumab:

   Selected advanced solid tumors: colorectal cancer, gastric-esophageal cancer, ovarian /fallopian tube cancer, pancreatic cancer, non-small cell lung cancer, and melanoma.

   Note: For colorectal cancer, gastric-esophageal cancer, ovarian/fallopian tube cancer, pancreatic cancers mismatch repair (MMR) / microsatellite stability (MSS) / microsatellite instability (MSI) status is mandatory. If MMR/MSS/MSI status is not available at signature of the informed consent, the test should be performed before Cycle 1 Day 1 (C1D1).

   Part 2 Dose expansion camidanlumab tesirine in combination with pembrolizumab:

   • Group 1: One of the indications identified in Part 1, for which at least 1 response (PR or CR) was seen.
   • Group 2: Patients with advanced solid tumors and MSI-H/dMMR status, who have received a prior regimen containing PD-1/PD-L1 inhibitors, for which the best response was CR, PR, or SD ≥4 months, and then progressed while under treatment with the PD-1/PD-L1 inhibitor-based regimen.

   Note: A maximum of 4 patients with the same indication will be allowed in this basket group.

4. Patients who are refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
5. Patients with advanced/metastatic cancer, with measurable disease as determined by RECIST v1.1 or immune-related Response Criteria (irRC)/ immune-related Response Evaluation Criteria In Solid Tumors (irRECIST)/ immune-related Response Evaluation Criteria In Solid Tumors (iRECIST)/ immune-modified Response Evaluation Criteria in Solid Tumors (imRECIST) as per Investigator discretion.

6. A) For camidanlumab tesirine as monotherapy: Patient must have a site of disease amenable to biopsy and be willing to undergo fresh biopsy procedures (minimum 3 passes each) prior to first dose, according to the treating institution's guidelines.

   B) Patients included in the paired-biopsy cohort must in addition be willing to undergo fresh biopsy procedures (minimum 3 passes each) after receiving at least 1 dose of study drug.

   C) For camidanlumab tesirine in combination with pembrolizumab: Patient must either have a site of disease amenable to biopsy and must provide fresh tumor biopsy prior to C1D1, or have sufficient available archival tumor tissue (biopsied after their last disease progression, and in the situation where the patient has received no additional anti-cancer therapy between their progression and C1D1). Patients must also be willing to undergo fresh biopsy procedures (minimum 3 passes each) after receiving at least 1 dose of study treatment, according to the treating institution's guidelines.

7. ECOG performance status 0-1.
8. Patient with life expectancy ≥ 3 months as per Investigator assessment.

9. Adequate organ function as defined by screening laboratory values within the following parameters:

   1. Absolute neutrophil count (ANC) ≥ 1.5 × 10^3/μL (off growth factors at least 72 hours).
   2. Platelet count ≥100 × 10^3/μL without transfusion in the past 10 days.
   3. Hemoglobin ≥9 g/dL (5.6 mmol/L) (prior transfusion allowed).
   4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma glutamyl transferase (GGT) ≤2.5 × the upper limit of normal (ULN) if there is no liver involvement; ALT or AST ≤5 × ULN if there is liver involvement.
   5. Total bilirubin ≤1.5 × ULN (patients with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN with direct bilirubin ≤1.5 × ULN).
   6. Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the Cockcroft-Gault equation.
10. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drug for women of childbearing potential (WOCBP).
11. Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 9.5 months after the last dose of camidanlumab tesirine or 4 months after last dose of pembrolizumab, whichever is the latest. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent until at least 6.5 months after the patient receives his last dose of camidanlumab tesirine or 4 months after last dose of pembrolizumab, whichever is the latest.

Exclusion Criteria:

1. Participation in another investigational interventional study.
2. Prior therapy with a CD25 (IL-2R) antibody.
3. Known history of ≥Grade 3 hypersensitivity to a therapeutic antibody.
4. Patients with prior solid organ or allogeneic bone marrow transplant.
5. History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjögren's syndrome, autoimmune vasculitis [e.g., Wegener's granulomatosis]) (patients with vitiligo, type 1 diabetes mellitus, residual hypothyroidism, hypophysitis due to autoimmune condition only requiring hormone replacement may be enrolled).
6. History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy including Guillain-Barré syndrome and myasthenia gravis) or other central nervous system (CNS) autoimmune disease (e.g., poliomyelitis, multiple sclerosis).

7. History of recent infection (within 4 weeks of C1D1) caused by a pathogen known to be associated with GBS, for example: herpes simplex virus 1/2 (HSV1, HSV2), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, enterovirus D68, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

   Note: An influenza test and a pathogen-directed SARS-CoV-2 test (such as polymerase chain reaction [PCR]) are mandatory and must be negative before initiating study treatment (tests to be performed 3 days or less prior to dosing on C1D1; an additional 2 days are allowed in the event of logistical issues for receiving the results on time).

8. Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV). Note: Testing is not mandatory to be eligible but should be considered in patients with high risk for these infections; testing is mandatory if status is unknown.
9. History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
10. Failure to recover to ≤Grade 1 (Common Terminology Criteria for Adverse Events version 4.0 [CTCAE version 4.0]) from acute nonhematologic toxicity (to ≤Grade 2 for neuropathy or alopecia), due to previous therapy, prior to screening.
11. Symptomatic CNS metastases or evidence of leptomeningeal disease (brain MRI or previously documented cerebrospinal fluid [CSF] cytology). Previously treated asymptomatic CNS metastases are permitted provided that the last treatment (systemic anticancer therapy and/or local radiotherapy) was completed ≥4 weeks prior to Day 1 except usage of low dose of steroids on a taper (i.e., up to 10 mg prednisone or equivalent on Day 1 and consecutive days is permissible if being tapered down). Patients with discrete dural metastases are eligible.
12. Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath).
13. Active diarrhea CTCAE Grade 2 or a medical condition associated with chronic diarrhea (such as irritable bowel syndrome, inflammatory bowel disease).
14. Active infection requiring systemic antibiotic therapy.
15. Active bleeding diathesis or significant anticoagulation (international normalized ratio [INR] ≥2.0).
16. Breastfeeding or pregnant.
17. Significant medical comorbidities, including uncontrolled hypertension (blood pressure [BP] ≥160 mmHg systolic and/or ≥110 mmHg diastolic repeatedly with or without anti hypertensive medication), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, severe uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, active ulceration of the upper gastrointestinal (GI) tract or GI bleeding, or severe chronic pulmonary disease.
18. Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor. For cytotoxic agents that have major delayed toxicity, e.g., mitomycin C and nitrosoureas, 4 weeks is indicated as washout period. For patients receiving systemic anticancer immunotherapies (as opposed to intralesional) that lead to activation of Teffs and/or increase the Teff/Treg ratio, such as anti-PD-1 antibodies, 4 weeks are indicated as the washout period.
19. Use of any other experimental medication within 14 days prior to start of study drug (C1D1).

20. Patients requiring concomitant immunosuppressive agents or chronic treatment with corticosteroids except:

    • replacement dose steroids in the setting of adrenal insufficiency
    • topical, inhaled, nasal, and ophthalmic steroids are allowed.
21. Planned live vaccine within 30 days prior to the first dose of study treatment and during study treatment.
22. Congenital long QT syndrome, or a corrected QTcF interval of ≥ 480 ms, at screening (unless secondary to pacemaker or bundle branch block).
23. Active second primary malignancy other than non-melanoma skin cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree and document should not be exclusionary.
24. Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the patient inappropriate for study participation or put the patient at risk.
25. For patients treated with camidanlumab tesirine in combination with pembrolizumab: patients intolerant to checkpoint-inhibitor or with a history of the following ≥ Grade 3 immune-related adverse events: hepatitis, renal, ocular, neurologic, cardiovascular, rheumatologic, and hematologic.
26. For patient treated with camidanlumab tesirine in combination with pembrolizumab: patients with a history of non-infectious pneumonitis related to prior systemic treatment and that require treatment with steroids within the last 6 months prior to enrollment.

Contacts and Locations

Locations

United States, California

Stanford Cancer Center

Palo Alto, California, United States, 94304

United States, Connecticut

Smilow Cancer Hospital Phase 1 Unit

New Haven, Connecticut, United States, 06511

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Tennessee

The Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

United States, Texas

The START Center for Cancer Care

San Antonio, Texas, United States, 78229

Belgium

Institut Jules Bordet

Anderlecht, Belgium, B-1070

Universitair Ziekenhuis Gent

Gent, Belgium, 9000

United Kingdom

University College London Hospitals NHS Foundation Trust

London, England, United Kingdom, NW1 2PG

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

Sponsors and Collaborators

ADC Therapeutics S.A.

More Information

• Responsible Party: ADC Therapeutics S.A.
• ClinicalTrials.gov Identifier: NCT03621982
• Other Study ID Numbers: ADCT-301-103; 2019-003132-23 ( EudraCT Number )
• First Posted: August 9, 2018
• Last Update Posted: March 17, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ADC Therapeutics S.A.:

Camidanlumab tesirine

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Triple Negative Breast Neoplasms; Fallopian Tube Neoplasms; Pancreatic Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Digestive System Neoplasms; Digestive System Diseases; Urologic Neoplasms; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Kidney Neoplasms; Kidney Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases