Ovarian Cancer, Solid Tumors
Conditions
Brief summary
ALM201/0001 is a Phase I, open-label, dose-escalation study of the safety, tolerability and pharmacokinetics (PK) of ALM201. Part 1 will be a dose-escalation study. Patients with advanced solid tumours will receive daily doses of ALM201 on Days 1-5, 8-12 and 15-19 in 21 day cycles. Part 2 will be a dose-expansion of the Maximum Tolerated Dose (MTD) determined in Part 1. Patients with advanced ovarian cancer will be enrolled with the main objective to determine the recommended Phase II dose.
Detailed description
ALM201 is a peptide with anti-angiogenic activity in a range of in-vitro and ex-vivo models. ALM201/0001 is a Phase I, multicentre, open-label, dose-escalation study of the safety, tolerability and pharmacokinetics (PK) of ALM201. The study is divided into two parts. Part 1 will enrol patients with advanced solid tumours. Patients will receive subcutaneous injection of ALM201 on Days 1-5, 8-12 and 15-19 in 21 day cycles. Patients can receive up to 8 cycles of treatment. Enrolment will follow an accelerated dose-escalation schedule until grade 2 drug-related adverse events are observed, at this point the 3+3 enrolment design will be used. There will be at least 1 week stagger between the first and subsequent patients in a new cohort dose. Dose increments will not exceed 100% escalation and will be guided by data generated from previous cycles. The dose and possibly the schedule will be adjusted to determine the Maximum Tolerated Dose (MTD). Part 2 will enrol patients with advanced ovarian cancer whose tumour has a proangiogenic profile as assessed by an angiogenesis gene signature biomarker. Patients will receive ALM201 at a dose and schedule established in Part 1. Patients will undergo safety and tumour assessments as well as blood draws for PK profiling. The safety assessments will involve physical examination, vital signs, biochemistry and haematology laboratory screens as well as immunogenicity testing. Tumour assessments will involve computed tomography (CT) or magnetic resonance imaging (MRI) scans at screening and after every 2 cycles during cycles 1 -8. Patients will be asked to provide consent for access to archived tumour tissue and for fresh biopsies to be taken at pre-dose, tumour response and/or point of disease progression for potential biomarker and pharmacodynamic assessments. PK profiling will be carried out in Cycles 1, 2, 4, 6 and 8.
Interventions
DRUGALM201
Drug: ALM201 administered subcutaneously
Sponsors
Almac Discovery
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Part 1 Specific Inclusion Criterion \*Patients with histologically and/or cytologically confirmed advanced solid tumour for whom no standard effective therapy is available or felt likely to be of limited efficacy and in whom a rationale for use of an anti-angiogenic treatment approach exists. Note: Previous use of anti-angiogenic therapy is allowed if tolerated * Part 2 Specific Inclusion Criterion \*Patients with advanced ovarian cancer, who are intolerant of or whose tumour is resistant to platinums and who have failed to respond to, or have relapsed following, standard therapy and whose tumour has a proangiogenic profile as assessed by the angiogenesis gene signature test. Note: Previous use of anti-angiogenic therapy is allowed if tolerated. * General Inclusion Criteria for all Patients * Measurable or evaluable disease. * Recovery from previous treatment to baseline or CTCAE ≤ Grade 1, as determined by CTCAE v4.03 criteria (Appendix B), of reversible toxicities related to prior treatment, with the exception of alopecia, lymphopenia, other non-clinically significant adverse events; recovery from previous radiotherapy other than residual cutaneous effects or stable \< Grade 2 gastrointestinal toxicity; complete recovery from surgery other than stable \< Grade 2 toxicity. * ECOG Performance Status (PS) of 0 or 1. * Acceptable haematological, renal and hepatic * Women must have either a negative pregnancy test prior to first study drug administration or be post menopausal. Male and female patients of childbearing potential must use appropriate methods birth control. * Patients must give written informed consent and understand the requirements of the study
Exclusion criteria
For all Patients * History of inability to tolerate anti-angiogenic therapies e.g. increased blood pressure (BP), proteinuria, prior thromboembolic events. * Previous history of bowel obstruction, clinical evidence of gastro-intestinal obstruction, large burden of peritoneal disease or evidence of bowel involvement on computed tomography. * Patents has received: * any chemotherapy regimens (including investigational agents) with delayed toxicity within 4 weeks (6 weeks for prior nitrosourea or mitomycin C) of Cycle 1, Day 1, or received chemotherapy regimens given continuously or on a weekly basis which have limited potential for delayed toxicity within 2 weeks of Cycle 1, Day 1. * radiotherapy, immunotherapy or biological agents (includes investigational agents) within 4 weeks of Cycle 1, Day 1. Localised palliative radiotherapy is permitted for symptom control. * Documented, symptomatic or uncontrolled intracranial metastases or primary intracerebral tumours. * Cancer with leptomeningeal involvement. * On therapeutic anti-coagulation (aspirin dosing ≤100 mg per oral (PO) daily allowed). * Previous malignancy, except for non-basal-cell carcinoma of skin or carcinoma-in-situ of the uterine cervix, unless the tumour was treated with curative intent more than 2 years prior to study entry. * Active cardiac condition or history of significant cardiac condition. Known human immunodeficiency virus positivity. * Active hepatitis B or C or other active liver disease (other than malignancy). * Any active, clinically significant, viral, bacterial, or systemic fungal infection within 4 weeks prior to Cycle 1, Day 1. * Any evidence of severe or uncontrolled systemic conditions or any other issues which make it undesirable for the patient to participate in the study or which could jeopardize compliance with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability - Evaluation of AEs and DLT | Adverse event evaluation was done during treatment and follow-up. DLT evaluation was done during cycle 1 | All events and suspected dose limiting toxicities (DLTs) were graded according to the CTCAE, version 4.03. A DLT was defined as a Grade 3 or 4 AE that, in the opinion of the CRC, was likely to be related to ALM201 and represented a clinically significant hazard to the patient. Qualifying DLT events were considered to be clinically relevant; e.g. in duration, apparent reversibility, required management, and upon consideration of the patient's medical history and/or concomitant medications. DLT events were also evaluated in terms of what was considered to be an appropriate next escalation step: In the case where the CRC agreed that an escalation step of approximately 33% or lower was merited; the toxicity of concern could be declared a DLT. In order to be evaluable for DLT assessment, a patient had to receive at least 80% of their scheduled doses (e.g. 12 of the 15), unless this lack of compliance was due to ALM201-related toxicity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tumour Response Assessment - Best Overall Response | Response assessments were done to assess clinical benefit in the efficacy population overall and at the end of cycles 2, 4 and 6, as applicable | As this was a Phase 1 study, the extent of efficacy data was expected to be limited. Using RECIST Version 1.1, a summary of clinical benefit from patients with evaluable disease was generated via CT scans: Complete Response (CR) = Disappearance of all target & non-target lesions + normalization of tumor marker; Partial Response (PR) ≥ 30% decrease in the sum of LD of target lesions; Progressive Disease (PD) ≥ 20% increase (& 5mm absolute increase) in sum of LD of target lesions or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions; Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD or persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. |
| Pharmacokinetics: Tmax | Tmax was determined in cycles 1, 2, 4 and 6 of treatment | Tmax was derived from the individual patient plasma concentration versus time profiles of ALM201. |
| Pharmacokinetics: AUC 0-t | AUC 0-t was determined in cycles 1, 2, 4 and 6 of treatment | AUC 0-t was derived from the individual patient plasma concentration versus time profiles of ALM201. |
| Pharmacokinetics: Cmax | Cmax of ALM201 following subcutaneous (SC) administration of ALM201 was determined in cycles 1, 2, 4 and 6 of treatment | Cmax was derived from the individual patient plasma concentration of ALM201. |
Countries
United Kingdom
Participant flow
Recruitment details
Recruitment was carried out in three study sites in Belfast, Manchester and Newcastle, UK starting on 27 April 2015.
Pre-assignment details
Part 1 enrolled adult patients with advanced solid tumours in whom treatment with an anti-angiogenic agent was appropriate. Participants had screening evaluations between Day -1 and -28 before entering the first 21-day treatment cycle.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 - ALM201 One patient received 10 mg IMP from cycle 1 through cycle 6. | 1 |
| Cohort 2 - ALM201 One patient received 20 mg IMP in cycle 1 and cycle 2. | 1 |
| Cohort 3 - ALM201 One patient received 40 mg IMP from cycle 1 through cycle 3. | 1 |
| Cohort 4 - ALM201 Three patients received 80 mg IMP (3 patients during cycle 1, 2 patients in cycle 1 and cycle 2). | 3 |
| Cohort 5 - ALM201 Three patients received 160 mg of IMP in cycles 1 and 2. | 3 |
| Cohort 6 - ALM201 Four patients received 200 mg IMP in cycle 1; 3 patients in cycle 1 and 2, 2 patients in cycle 1 through 4 and one patient in cycle 1 through 5. | 4 |
| Cohort 7 - ALM201 Three patients received 300 mg IMP in cycle 1 and 2; one of them received the IMP in cycle 1 through cycle 6. | 3 |
| Cohort 8 - ALM201 Four patients received 100 mg IMP in cycle 1; two of them completed cycle 2. | 4 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Disease Progression | 1 | 1 | 1 | 3 | 3 | 4 | 2 | 3 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Cohort 2 - ALM201 | Cohort 3 - ALM201 | Cohort 4 - ALM201 | Cohort 1 - ALM201 | Cohort 5 - ALM201 | Cohort 6 - ALM201 | Cohort 7 - ALM201 | Cohort 8 - ALM201 |
|---|---|---|---|---|---|---|---|---|---|
| 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 | 6 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 2 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 | 0 Participants | 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 | 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 | 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 | 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 3 Participants | 4 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Female | 12 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 8 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 1 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 / 1 | 0 / 1 | 0 / 1 | 0 / 3 | 0 / 3 | 0 / 4 | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 1 / 1 | 0 / 1 | 1 / 1 | 3 / 3 | 3 / 3 | 4 / 4 | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 1 / 1 | 0 / 1 | 0 / 1 | 1 / 3 | 1 / 3 | 2 / 4 | 0 / 3 | 1 / 4 |
Outcome results
Primary
Safety and Tolerability - Evaluation of AEs and DLT
All events and suspected dose limiting toxicities (DLTs) were graded according to the CTCAE, version 4.03. A DLT was defined as a Grade 3 or 4 AE that, in the opinion of the CRC, was likely to be related to ALM201 and represented a clinically significant hazard to the patient. Qualifying DLT events were considered to be clinically relevant; e.g. in duration, apparent reversibility, required management, and upon consideration of the patient's medical history and/or concomitant medications. DLT events were also evaluated in terms of what was considered to be an appropriate next escalation step: In the case where the CRC agreed that an escalation step of approximately 33% or lower was merited; the toxicity of concern could be declared a DLT. In order to be evaluable for DLT assessment, a patient had to receive at least 80% of their scheduled doses (e.g. 12 of the 15), unless this lack of compliance was due to ALM201-related toxicity.
Time frame: Adverse event evaluation was done during treatment and follow-up. DLT evaluation was done during cycle 1
Population: Reporting group
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE treatment related | 1 participants |
| Cohort 1 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE DLT | 1 participants |
| Cohort 1 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | SAE | 0 participants |
| Cohort 1 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | treatment related SAE | 1 participants |
| Cohort 2 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | treatment related SAE | 0 participants |
| Cohort 2 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE DLT | 0 participants |
| Cohort 2 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE treatment related | 0 participants |
| Cohort 2 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | SAE | 0 participants |
| Cohort 3 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE treatment related | 1 participants |
| Cohort 3 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | treatment related SAE | 0 participants |
| Cohort 3 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE DLT | 1 participants |
| Cohort 3 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | SAE | 0 participants |
| Cohort 4 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE treatment related | 3 participants |
| Cohort 4 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE DLT | 1 participants |
| Cohort 4 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | SAE | 0 participants |
| Cohort 4 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | treatment related SAE | 1 participants |
| Cohort 5 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | treatment related SAE | 1 participants |
| Cohort 5 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | SAE | 0 participants |
| Cohort 5 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE DLT | 3 participants |
| Cohort 5 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE treatment related | 3 participants |
| Cohort 6 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | treatment related SAE | 2 participants |
| Cohort 6 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | SAE | 0 participants |
| Cohort 6 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE DLT | 4 participants |
| Cohort 6 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE treatment related | 4 participants |
| Cohort 7 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | treatment related SAE | 0 participants |
| Cohort 7 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE treatment related | 3 participants |
| Cohort 7 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | SAE | 0 participants |
| Cohort 7 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE DLT | 3 participants |
| Cohort 8 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE DLT | 2 participants |
| Cohort 8 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | SAE | 0 participants |
| Cohort 8 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | treatment related SAE | 1 participants |
| Cohort 8 - ALM201 | Safety and Tolerability - Evaluation of AEs and DLT | TEAE treatment related | 4 participants |
Secondary
Pharmacokinetics: AUC 0-t
AUC 0-t was derived from the individual patient plasma concentration versus time profiles of ALM201.
Time frame: AUC 0-t was determined in cycles 1, 2, 4 and 6 of treatment
Population: Reporting group
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 1 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 18 | 817 ng*h/mL |
| Cohort 1 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 1 | 485 ng*h/mL |
| Cohort 1 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 2 - Day 18 | 702 ng*h/mL |
| Cohort 1 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 6 - Day 18 | 1040 ng*h/mL |
| Cohort 1 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 3 | 868 ng*h/mL |
| Cohort 1 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 4 - Day 18 | 476 ng*h/mL |
| Cohort 2 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 1 | 1040 ng*h/mL |
| Cohort 2 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 3 | 1160 ng*h/mL |
| Cohort 2 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 18 | 718 ng*h/mL |
| Cohort 2 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 2 - Day 18 | 1020 ng*h/mL |
| Cohort 3 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 3 | 898 ng*h/mL |
| Cohort 3 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 2 - Day 18 | 1950 ng*h/mL |
| Cohort 3 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 1 | 1920 ng*h/mL |
| Cohort 3 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 18 | 1840 ng*h/mL |
| Cohort 4 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 18 | 3500 ng*h/mL |
| Cohort 4 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 2 - Day 18 | 3230 ng*h/mL |
| Cohort 4 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 3 | 2970 ng*h/mL |
| Cohort 4 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 1 | 3380 ng*h/mL |
| Cohort 5 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 1 | 6510 ng*h/mL |
| Cohort 5 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 18 | 4930 ng*h/mL |
| Cohort 5 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 3 | 5100 ng*h/mL |
| Cohort 5 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 2 - Day 18 | 5710 ng*h/mL |
| Cohort 6 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 1 | 5860 ng*h/mL |
| Cohort 6 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 3 | 6630 ng*h/mL |
| Cohort 6 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 2 - Day 18 | 5680 ng*h/mL |
| Cohort 6 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 4 - Day 18 | 6110 ng*h/mL |
| Cohort 6 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 18 | 5570 ng*h/mL |
| Cohort 7 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 6 - Day 18 | 26700 ng*h/mL |
| Cohort 7 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 1 | 11900 ng*h/mL |
| Cohort 7 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 3 | 12500 ng*h/mL |
| Cohort 7 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 18 | 12100 ng*h/mL |
| Cohort 7 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 2 - Day 18 | 10400 ng*h/mL |
| Cohort 7 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 4 - Day 18 | 8600 ng*h/mL |
| Cohort 8 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 1 | 6280 ng*h/mL |
| Cohort 8 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 2 - Day 18 | 5930 ng*h/mL |
| Cohort 8 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 18 | 8100 ng*h/mL |
| Cohort 8 - ALM201 | Pharmacokinetics: AUC 0-t | Cycle 1 - Day 3 | 8870 ng*h/mL |
Secondary
Pharmacokinetics: Cmax
Cmax was derived from the individual patient plasma concentration of ALM201.
Time frame: Cmax of ALM201 following subcutaneous (SC) administration of ALM201 was determined in cycles 1, 2, 4 and 6 of treatment
Population: Reporting group
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort 1 - ALM201 | Pharmacokinetics: Cmax | Cycle 2 - Day 18 | 288 ng/mL |
| Cohort 1 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 1 | 200 ng/mL |
| Cohort 1 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 3 | 406 ng/mL |
| Cohort 1 - ALM201 | Pharmacokinetics: Cmax | Cycle 6 - Day 18 | 470 ng/mL |
| Cohort 1 - ALM201 | Pharmacokinetics: Cmax | Cycle 4 - Day 18 | 193 ng/mL |
| Cohort 1 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 18 | 352 ng/mL |
| Cohort 2 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 3 | 614 ng/mL |
| Cohort 2 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 18 | 319 ng/mL |
| Cohort 2 - ALM201 | Pharmacokinetics: Cmax | Cycle 2 - Day 18 | 394 ng/mL |
| Cohort 2 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 1 | 542 ng/mL |
| Cohort 3 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 18 | 405 ng/mL |
| Cohort 3 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 1 | 592 ng/mL |
| Cohort 3 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 3 | 759 ng/mL |
| Cohort 3 - ALM201 | Pharmacokinetics: Cmax | Cycle 2 - Day 18 | 583 ng/mL |
| Cohort 4 - ALM201 | Pharmacokinetics: Cmax | Cycle 2 - Day 18 | 849 ng/mL |
| Cohort 4 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 18 | 1090 ng/mL |
| Cohort 4 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 3 | 861 ng/mL |
| Cohort 4 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 1 | 835 ng/mL |
| Cohort 5 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 1 | 1990 ng/mL |
| Cohort 5 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 3 | 1490 ng/mL |
| Cohort 5 - ALM201 | Pharmacokinetics: Cmax | Cycle 2 - Day 18 | 1870 ng/mL |
| Cohort 5 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 18 | 1350 ng/mL |
| Cohort 6 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 3 | 1620 ng/mL |
| Cohort 6 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 18 | 1670 ng/mL |
| Cohort 6 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 1 | 1490 ng/mL |
| Cohort 6 - ALM201 | Pharmacokinetics: Cmax | Cycle 2 - Day 18 | 1890 ng/mL |
| Cohort 6 - ALM201 | Pharmacokinetics: Cmax | Cycle 4 - Day 18 | 1680 ng/mL |
| Cohort 7 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 3 | 2690 ng/mL |
| Cohort 7 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 1 | 2550 ng/mL |
| Cohort 7 - ALM201 | Pharmacokinetics: Cmax | Cycle 4 - Day 18 | 2140 ng/mL |
| Cohort 7 - ALM201 | Pharmacokinetics: Cmax | Cycle 6 - Day 18 | 6830 ng/mL |
| Cohort 7 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 18 | 2880 ng/mL |
| Cohort 7 - ALM201 | Pharmacokinetics: Cmax | Cycle 2 - Day 18 | 2780 ng/mL |
| Cohort 8 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 1 | 1810 ng/mL |
| Cohort 8 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 3 | 2750 ng/mL |
| Cohort 8 - ALM201 | Pharmacokinetics: Cmax | Cycle 2 - Day 18 | 1790 ng/mL |
| Cohort 8 - ALM201 | Pharmacokinetics: Cmax | Cycle 1 - Day 18 | 2330 ng/mL |
Secondary
Pharmacokinetics: Tmax
Tmax was derived from the individual patient plasma concentration versus time profiles of ALM201.
Time frame: Tmax was determined in cycles 1, 2, 4 and 6 of treatment
Population: Reporting group
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1 - ALM201 | Pharmacokinetics: Tmax | Cycle 2 - Day 18 | 2.00 hour |
| Cohort 1 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 1 | 1.45 hour |
| Cohort 1 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 3 | 0.50 hour |
| Cohort 1 - ALM201 | Pharmacokinetics: Tmax | Cycle 6 - Day 18 | 1.85 hour |
| Cohort 1 - ALM201 | Pharmacokinetics: Tmax | Cycle 4 - Day 18 | 1.53 hour |
| Cohort 1 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 18 | 1.58 hour |
| Cohort 2 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 3 | 1.00 hour |
| Cohort 2 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 18 | 1.02 hour |
| Cohort 2 - ALM201 | Pharmacokinetics: Tmax | Cycle 2 - Day 18 | 1.00 hour |
| Cohort 2 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 1 | 1.50 hour |
| Cohort 3 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 18 | 1.00 hour |
| Cohort 3 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 1 | 1.63 hour |
| Cohort 3 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 3 | 1.50 hour |
| Cohort 3 - ALM201 | Pharmacokinetics: Tmax | Cycle 2 - Day 18 | 1.03 hour |
| Cohort 4 - ALM201 | Pharmacokinetics: Tmax | Cycle 2 - Day 18 | 3.50 hour |
| Cohort 4 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 18 | 1.23 hour |
| Cohort 4 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 3 | 1.50 hour |
| Cohort 4 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 1 | 1.53 hour |
| Cohort 5 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 1 | 1.52 hour |
| Cohort 5 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 3 | 1.52 hour |
| Cohort 5 - ALM201 | Pharmacokinetics: Tmax | Cycle 2 - Day 18 | 2.00 hour |
| Cohort 5 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 18 | 1.50 hour |
| Cohort 6 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 3 | 2.00 hour |
| Cohort 6 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 18 | 2.03 hour |
| Cohort 6 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 1 | 2.50 hour |
| Cohort 6 - ALM201 | Pharmacokinetics: Tmax | Cycle 2 - Day 18 | 1.54 hour |
| Cohort 6 - ALM201 | Pharmacokinetics: Tmax | Cycle 4 - Day 18 | 1.57 hour |
| Cohort 7 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 3 | 1.02 hour |
| Cohort 7 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 1 | 2.00 hour |
| Cohort 7 - ALM201 | Pharmacokinetics: Tmax | Cycle 4 - Day 18 | 1.12 hour |
| Cohort 7 - ALM201 | Pharmacokinetics: Tmax | Cycle 6 - Day 18 | 2.02 hour |
| Cohort 7 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 18 | 1.50 hour |
| Cohort 7 - ALM201 | Pharmacokinetics: Tmax | Cycle 2 - Day 18 | 2.00 hour |
| Cohort 8 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 1 | 1.50 hour |
| Cohort 8 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 3 | 1.61 hour |
| Cohort 8 - ALM201 | Pharmacokinetics: Tmax | Cycle 2 - Day 18 | 1.02 hour |
| Cohort 8 - ALM201 | Pharmacokinetics: Tmax | Cycle 1 - Day 18 | 1.90 hour |
Secondary
Tumour Response Assessment - Best Overall Response
As this was a Phase 1 study, the extent of efficacy data was expected to be limited. Using RECIST Version 1.1, a summary of clinical benefit from patients with evaluable disease was generated via CT scans: Complete Response (CR) = Disappearance of all target & non-target lesions + normalization of tumor marker; Partial Response (PR) ≥ 30% decrease in the sum of LD of target lesions; Progressive Disease (PD) ≥ 20% increase (& 5mm absolute increase) in sum of LD of target lesions or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions; Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD or persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits.
Time frame: Response assessments were done to assess clinical benefit in the efficacy population overall and at the end of cycles 2, 4 and 6, as applicable
Population: Reporting group
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 - ALM201 | Tumour Response Assessment - Best Overall Response | Disease Control Rate (CR+PR+SD) | 1 participants |
| Cohort 1 - ALM201 | Tumour Response Assessment - Best Overall Response | Progressive Disease | 0 participants |
| Cohort 1 - ALM201 | Tumour Response Assessment - Best Overall Response | Overall Response Rate (CR+PR) | 0 participants |
| Cohort 1 - ALM201 | Tumour Response Assessment - Best Overall Response | Complete Response (CR) | 0 participants |
| Cohort 1 - ALM201 | Tumour Response Assessment - Best Overall Response | Partial Response (PR) | 0 participants |
| Cohort 1 - ALM201 | Tumour Response Assessment - Best Overall Response | Stable Disease (SD) | 1 participants |
| Cohort 1 - ALM201 | Tumour Response Assessment - Best Overall Response | Not Evaluable (NE+NA) | 0 participants |
| Cohort 2 - ALM201 | Tumour Response Assessment - Best Overall Response | Not Evaluable (NE+NA) | 0 participants |
| Cohort 2 - ALM201 | Tumour Response Assessment - Best Overall Response | Disease Control Rate (CR+PR+SD) | 0 participants |
| Cohort 2 - ALM201 | Tumour Response Assessment - Best Overall Response | Partial Response (PR) | 0 participants |
| Cohort 2 - ALM201 | Tumour Response Assessment - Best Overall Response | Overall Response Rate (CR+PR) | 0 participants |
| Cohort 2 - ALM201 | Tumour Response Assessment - Best Overall Response | Stable Disease (SD) | 0 participants |
| Cohort 2 - ALM201 | Tumour Response Assessment - Best Overall Response | Complete Response (CR) | 0 participants |
| Cohort 2 - ALM201 | Tumour Response Assessment - Best Overall Response | Progressive Disease | 1 participants |
| Cohort 3 - ALM201 | Tumour Response Assessment - Best Overall Response | Disease Control Rate (CR+PR+SD) | 1 participants |
| Cohort 3 - ALM201 | Tumour Response Assessment - Best Overall Response | Not Evaluable (NE+NA) | 0 participants |
| Cohort 3 - ALM201 | Tumour Response Assessment - Best Overall Response | Stable Disease (SD) | 1 participants |
| Cohort 3 - ALM201 | Tumour Response Assessment - Best Overall Response | Partial Response (PR) | 0 participants |
| Cohort 3 - ALM201 | Tumour Response Assessment - Best Overall Response | Complete Response (CR) | 0 participants |
| Cohort 3 - ALM201 | Tumour Response Assessment - Best Overall Response | Progressive Disease | 0 participants |
| Cohort 3 - ALM201 | Tumour Response Assessment - Best Overall Response | Overall Response Rate (CR+PR) | 0 participants |
| Cohort 4 - ALM201 | Tumour Response Assessment - Best Overall Response | Stable Disease (SD) | 0 participants |
| Cohort 4 - ALM201 | Tumour Response Assessment - Best Overall Response | Not Evaluable (NE+NA) | 0 participants |
| Cohort 4 - ALM201 | Tumour Response Assessment - Best Overall Response | Partial Response (PR) | 0 participants |
| Cohort 4 - ALM201 | Tumour Response Assessment - Best Overall Response | Progressive Disease | 3 participants |
| Cohort 4 - ALM201 | Tumour Response Assessment - Best Overall Response | Overall Response Rate (CR+PR) | 0 participants |
| Cohort 4 - ALM201 | Tumour Response Assessment - Best Overall Response | Complete Response (CR) | 0 participants |
| Cohort 4 - ALM201 | Tumour Response Assessment - Best Overall Response | Disease Control Rate (CR+PR+SD) | 0 participants |
| Cohort 5 - ALM201 | Tumour Response Assessment - Best Overall Response | Stable Disease (SD) | 0 participants |
| Cohort 5 - ALM201 | Tumour Response Assessment - Best Overall Response | Complete Response (CR) | 0 participants |
| Cohort 5 - ALM201 | Tumour Response Assessment - Best Overall Response | Partial Response (PR) | 0 participants |
| Cohort 5 - ALM201 | Tumour Response Assessment - Best Overall Response | Overall Response Rate (CR+PR) | 0 participants |
| Cohort 5 - ALM201 | Tumour Response Assessment - Best Overall Response | Disease Control Rate (CR+PR+SD) | 0 participants |
| Cohort 5 - ALM201 | Tumour Response Assessment - Best Overall Response | Progressive Disease | 3 participants |
| Cohort 5 - ALM201 | Tumour Response Assessment - Best Overall Response | Not Evaluable (NE+NA) | 0 participants |
| Cohort 6 - ALM201 | Tumour Response Assessment - Best Overall Response | Stable Disease (SD) | 2 participants |
| Cohort 6 - ALM201 | Tumour Response Assessment - Best Overall Response | Not Evaluable (NE+NA) | 1 participants |
| Cohort 6 - ALM201 | Tumour Response Assessment - Best Overall Response | Disease Control Rate (CR+PR+SD) | 2 participants |
| Cohort 6 - ALM201 | Tumour Response Assessment - Best Overall Response | Overall Response Rate (CR+PR) | 0 participants |
| Cohort 6 - ALM201 | Tumour Response Assessment - Best Overall Response | Progressive Disease | 1 participants |
| Cohort 6 - ALM201 | Tumour Response Assessment - Best Overall Response | Partial Response (PR) | 0 participants |
| Cohort 6 - ALM201 | Tumour Response Assessment - Best Overall Response | Complete Response (CR) | 0 participants |
| Cohort 7 - ALM201 | Tumour Response Assessment - Best Overall Response | Partial Response (PR) | 0 participants |
| Cohort 7 - ALM201 | Tumour Response Assessment - Best Overall Response | Complete Response (CR) | 0 participants |
| Cohort 7 - ALM201 | Tumour Response Assessment - Best Overall Response | Progressive Disease | 1 participants |
| Cohort 7 - ALM201 | Tumour Response Assessment - Best Overall Response | Disease Control Rate (CR+PR+SD) | 2 participants |
| Cohort 7 - ALM201 | Tumour Response Assessment - Best Overall Response | Not Evaluable (NE+NA) | 0 participants |
| Cohort 7 - ALM201 | Tumour Response Assessment - Best Overall Response | Overall Response Rate (CR+PR) | 0 participants |
| Cohort 7 - ALM201 | Tumour Response Assessment - Best Overall Response | Stable Disease (SD) | 2 participants |
| Cohort 8 - ALM201 | Tumour Response Assessment - Best Overall Response | Not Evaluable (NE+NA) | 0 participants |
| Cohort 8 - ALM201 | Tumour Response Assessment - Best Overall Response | Stable Disease (SD) | 1 participants |
| Cohort 8 - ALM201 | Tumour Response Assessment - Best Overall Response | Progressive Disease | 3 participants |
| Cohort 8 - ALM201 | Tumour Response Assessment - Best Overall Response | Complete Response (CR) | 0 participants |
| Cohort 8 - ALM201 | Tumour Response Assessment - Best Overall Response | Overall Response Rate (CR+PR) | 0 participants |
| Cohort 8 - ALM201 | Tumour Response Assessment - Best Overall Response | Disease Control Rate (CR+PR+SD) | 1 participants |
| Cohort 8 - ALM201 | Tumour Response Assessment - Best Overall Response | Partial Response (PR) | 0 participants |