PROTOCOL ADCT-601-102
Research type
Research Study
Full title
A Phase 1b, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Mipasetamab Uzoptirine (ADCT-601) Monotherapy and in Combination with Other Anti-Cancer Therapies in Patients with Selected Advanced Solid Tumors
IRAS ID
1005850
Contact name
Viet-Anh Do
Contact email
Sponsor organisation
ADC Therapeutics SA
Eudract number
2021-005566-18
Clinicaltrials.gov Identifier
Research summary
The aim of the study to find a safe and tolerable dose of a new experimental treatment called mipasetamab uzoptirine (ADCT-601), and to learn whether this treatment will be an effective treatment option for patients with selected advanced solid tumours. This study drug is an antibody-drug conjugate, meaning it is an antibody bound to an anti-cancer drug. In preclinical animal studies, data showed strong anti-tumour activity of ADCT-601 with gemcitabine. In a previous clinical study, ADCT-601 was found to be safe and generally well tolerated. This study is an open-label, phase 1b study that comprise of two parts namely, a dose escalation part and a dose expansion part. Both parts of the study will involve two arms and participants may receive either monotherapy (on its own) or combination therapy. The study will include a screening period, a treatment period and a follow-up period for up to 1 year after the end of treatment. Participants will receive treatment in cycles of 3 weeks as long as needed and/or tolerated. In the dose escalation part, the first three patients will start at a low dose. The second group of 3 patients receive a higher dose. Each new dose is thereafter increased after at least 3 patients have been dosed with no side effects. This dose escalation continues until a dose is identified as the dose to be used in the expansion part. ADCT-601 will be given as an intravenous (IV) infusion over 30 minutes on Day 1 of each cycle. Gemcitabine will be given as an IV infusion over 30 min on Day1 and Day 8 for 6 cycles. The response to the treatment will be assessed by radiographic tumour assessments and tumour markers. A Dose Escalation Steering Committee (DESC) will be responsible for safety monitoring and overall supervision of the study. The following study procedures will be performed: (a) physical examinations (b) ECGs (c) blood tests, (d) urine tests (e) CT/MRI/PET/Bone scans (f) tumour tissue collection (g) IV Infusion of study drugs
Summary of Results
The study was performed in 4 countries. One hundred and twenty-eight (128) patients were enrolled in the Study: 55 in the USA (6 sites), 11 in United-Kingdom (2 sites), 31 in France (4 sites) and 31 in Spain (3 sites).Patients were enrolled in different groups.
Part 1:
Arm A (ADCT-601 + gemcitabine): 23 with soft-tissue or bone sarcoma; 14 males (61%), 9 females (39%), median age of 46 years.
Arm B (ADCT-601): 32 with soft-tissue or bone sarcoma, or non-small cell lung cancer; 18 males (56%), 14 females (44%), median age of 56 years.
Part 2 Arm A (ADCT-601 + gemcitabine):Cohort 6: 11 with soft-tissue sarcoma; 1 male (9%), 10 females (91%), median age of 54 years.
Cohort 7: 26 with pancreatic cancer, 15 males (58%), 11 females (42%), median age of 62.5 years.
Part 2 Arm B (ADCT-601):Cohort 1: 17 with soft-tissue sarcoma; 9 males (53%), 8 females (47%), median age of 58 years.
Cohort 2: 19 with pancreatic cancer; 7 males (37%), 12 females (63%), median age of 62 years.
All patients received ADCT-601 and some also received gemcitabine. Both the patient and study staff knew which treatment was administered.
ADCT-601 was given as one treatment cycle every 3 weeks. Each patient was allowed to receive ADCT-601 until their cancer became worse, or until they were not able to tolerate ADCT-601 due to side effects, or the patient or their study doctor decided to stop treatment.For patients receiving gemcitabine together with ADCT-601, gemcitabine was given the first day and on day 8 of each cycle, every 3 weeks. Each patient who received gemcitabine was allowed to receive gemcitabine for 6 cycles, or until their cancer became worse, or until they were not able to tolerate gemcitabine due to side effects or the patient or their study doctor decided to stop treatment.
Part 1
Arm A: 23 patients received ADCT-601 at a dose level of 3.8 milligrams (mg), 7.5 mg, 11 mg or 13 mg, plus 1000 milligrams per square meter of body surface area (mg/m2) or 800 mg/m2 of gemcitabine.
Arm B: 32 patients received ADCT-601 at dose levels of 7.5 mg, 11 mg, 13 mg or 15 mg.
Part 2 Arm ACohort 6: 11 patients received ADCT-601 at a dose of 11 mg for the first dose then 9.5 mg for subsequent doses, plus 1000 mg/m2 of gemcitabine.
Cohort 7: 26 patients received ADCT-601 at dose level of 7.5 mg, 9.5 mg, 11 mg or 11 mg followed by 9.5 mg, plus 1000 mg/m2 of gemcitabine.
Part 2 Arm BCohort 1: 17 patients received ADCT-601 every 21 days at a dose of 13 mg for the first dose, then 11 mg for the subsequent doses, or every 28 days at a dose of 13 mg
Cohort 2: 19 patients received ADCT-601, at the dose level of 11 mg or 13 mg for the first dose, and then 11 mg for the subsequent doses
The patients enrolled in the study stopped the treatment either because their cancer became worse [67 patients (52%)], due to side effects [29 patients (23%)], the patient decided to stop [21 patients (16%)], study doctor asked them to stop [2 patients (2%)], or because they died [9 patients (7%)].Of the 126 patients who received ADCT-601 and had at least one scan, 8 patients (6%) had at least one scan showing their cancer had responded, 54 (43%) had stable disease and 47 (37%) had their disease progress.
In groups where patients received ADCT-601 alone (68 patients), the main side effects (>15 % of patients) considered related to ADCT-601 by physicians, were tiredness [17 patients (25%)]; collection of fluid around the lungs in the chest cavity, fluid retention in lower extremities [14 patients each (21% each)]; breathlessness, feeling sick, skin eruption of flat raised lesions [13 patients each (19% each)]; rash and numbness on the palms and soles [12 patients (18%)].
In the groups where patients received ADCT-601 plus gemcitabine (60 patients), the main side effects (>15 % of patients) considered related to ADCT-601 by physicians, were: decrease of platelets [36 patients (60%)]; decrease of red blood cells [34 patients (57%)]; decrease of neutrophils [33 patients (55%)]; tiredness [27 patients (45%)]; increase of a certain liver enzyme (alanine aminotransferase), feeling sick [16 patients each (27%)]; increase of a certain liver enzyme (aspartate aminotransferase) [15 patients (25%)]; weakness, collection of fluid around the lungs in the chest cavity, fluid retention in lower extremities [13 patients each (22%)]; increase of a certain liver enzyme (gamma-glutamyltransferase), rash [10 patients each (17%)]; breathlessness, increase of an enzyme in the body (blood alkaline phosphatase) [9 patients (16%)].
Certain side effects obliged some patients to delay, to reduce doses or to stop ADCT-601 and/or gemcitabine administration.
Due to the limited activity and the side effects observed, the Sponsor decided to stop the study early.
At this time, there is no plan for further development of ADCT-601.
REC name
East Midlands - Derby Research Ethics Committee
REC reference
22/EM/0235
Date of REC Opinion
19 Jan 2023
REC opinion
Further Information Favourable Opinion