Advanced Solid Tumors or Non-Hodgkin's Lymphoma (NHL)Phase 1/2NCT02797964
A Phase 1/2 Trial of SRA737 in Subjects With Advanced Cancer
A Phase 1/2 study testing SRA737 in people with Advanced Solid Tumors or Non-Hodgkin's Lymphoma (NHL), run by Sierra Oncology LLC - a GSK company at 15 sites in United Kingdom.
Trial summary
The purpose of this clinical study is to establish the safety profile, determine the maximum tolerated dose (MTD) and recommend a Phase 2 dose and schedule of SRA737; and to evaluate the efficacy of SRA737 in prospectively-selected subjects with genetically-defined tumors that harbor genomic alterations linked to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors or Non-Hodgkin's Lymphoma (NHL)
- What is being tested?
- SRA737
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 107 participants
- Where
- 15 sitesUnited Kingdom
- Study dates
- Jul 2016to 28 Oct 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- For Dose Escalation Only: any locally advanced or metastatic, histologically or cytologically proven solid tumor or NHL, relapsed after or progressing despite conventional treatment
- Life expectancy of at least 12 weeks
- World Health Organization (WHO) performance status of 0-1
- Must meet select hematological and biochemical laboratory indices
- Archival tumor tissue or accessible tumor and willingness to consent to a biopsy
- Expansion Only:
Show all 22Show fewer
- Any locally advanced or metastatic malignancy of the following types for which no other conventional therapy is considered appropriate:
- Metastatic Colorectal Cancer (CRC)
- Platinum-resistant or intolerant High Grade Serious Ovarian Cancer (HGSOC)
- Advanced Non-Small Cell Lung Cancer (NSCLC)
- Metastatic Castration-Resistant Prostate Cancer (mCRPC)
- Head and Neck Squamous Cell Carcinoma (HNSCC) or squamous cell carcinoma of the anus (SCCA).
- Eligibility may be further restricted by the select number of prior regimens specific to each indication
- Measurable disease per RECIST v1.1, or for mCRPC, evaluable disease per any of the following:
- Measurable disease per RECIST v1.1
- Increasing PSA
- Circulating tumor cell (CTC) count of 5 or more cells per 7.5 ml of blood
- Tumor tissue or ctDNA evidence that subject's tumor harbors a combination of mutations which are expected to confer sensitivity to Chk1 inhibition. Eligibility will be determined by the Sponsor's review of genetic abnormalities detected in genes in the following categories:
- Oncogenic drivers such as MYC, CCNE1, etc.
- Key tumor suppressor genes regulating G1 cell cycle progression/arrest such as RAD50, TP53, etc. For patients with NHSCC or SCCA, positive HPV status is also considered for eligibility.
- The DDR pathway including BRCA1, BRCA2 and FANC. For patients with CRC, MMR genetic alterations and/or high microsatellite instability are also considered for eligibility.
- Genetic indicators of replicative stress such as gain of function/amplification of Chk1 or ATR or other related gene.
Who cannot join
- Received the following prior or current anticancer therapy:
- Radiotherapy within the last 6 weeks
- Endocrine therapy during the previous 4 weeks
- Chemotherapy during the previous 4 weeks
- Immunotherapy during the previous 6 weeks
- Nitrosoureas or Mitomycin C during the previous 6 weeks
Show all 21Show fewer
- Other Investigational Medicinal Product during the 4 weeks before treatment
- Any prior treatment with a Chk1 inhibitor or prior treatment with an ATR inhibitor within 6 months prior to receiving SRA737
- Other malignancy within the past 2 years, except for adequately treated tumors
- Ongoing toxic manifestations of previous treatments greater than NCI-CTCAE Grade 1
- For Dose Escalation: new or progressing brain metastases. For Cohort Expansion: present or prior brain metastases
- High medical risk because of nonmalignant systemic disease
- Serologically positive for hepatitis B, hepatitis C or HIV
- Serious cardiac condition, left ventricular ejection fraction < 45% at baseline, history of cardiac ischemia within the past 6 months, or prior history of cardiac arrhythmia requiring treatment
- Prior bone marrow transplant or extensive radiotherapy to greater than 25% of bone marrow within 8 weeks
- Peanut allergy
- QTcF> 450 msec in adult males and > 470 msec in adult females
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of SRA737
- Inability to swallow capsules without chewing or crushing
- Is a participant or plans to participate in another interventional clinical trial
- Any other condition which in the Investigator's opinion would not make the subject a good candidate
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United Kingdom15 sites
The Clatterbridge Cancer Centre
Bebington, Wirral, CH63 4JY
Belfast City Hospital
Belfast, Northern Ireland, BT9 7AB
Velindre Cancer Centre - Cardiff
Cardiff, Whitchurch, CF14 2TL
Western General Hospital
Edinburgh, EH4 2XU
The Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
Oxford University Hospitals
Headington, Oxford, OX3 7LE
The Leeds Teaching Hospitals of St James University Hospital
Leeds, LS9 7TF
University Hospitals of Leicester
Leicester, LE1 5WW
Guy's and St. Thomas
London, SE1 9RT
Sarah Cannon Research Institute
London, W1G 6AD
University College London Hospitals
London, W1T 7HA
The Christie
Manchester, M20 4BX
Freeman Hospital
Newcastle upon Tyne, NE7 7DN
Sheffield Teaching Hospitals
Sheffield, S10 2SJ
Royal Marsden Hospital
Sutton, London, SM2 5PT
About this study
Official title: A Phase 1/2 Trial of SRA737 (a Chk1 Inhibitor) Administered Orally in Subjects With Advanced Cancer
The purpose of this clinical study is to establish the safety profile, determine the maximum tolerated dose (MTD) and recommend a Phase 2 dose and schedule of SRA737; and to evaluate the efficacy of SRA737 in prospectively-selected subjects with genetically-defined tumors that harbor genomic alterations linked to increased replication stress and that are hypothesized to be more sensitive to checkpoint kinase 1 (Chk1) inhibition via synthetic lethality. Specific cancer indications that frequently harbor these genetic mutations will be studied.
Read the detailed description
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Chk1, a key regulator of cell cycle progression and the DNA Damage Response (DDR) replication stress response. In cancer cells, intrinsic replication stress (RS) is induced by factors such as oncogenes (e.g., CCNE1 or MYC), genetic mutations in DNA repair machinery (e.g. BRCA1 or FANCA), genetic mutations leading to a dysregulated cell cycle (e.g., TP53 or RAD50) or other genomic alterations. This replication stress results in persistent DNA damage and genomic instability, leading to an increased dependency on Chk1 for survival. Targeted inhibition of Chk1 by SRA737 may therefore be synthetically lethal to cancer cells with elevated intrinsic RS.
This study has been designed to: establish the safety profile; determine the pharmacokinetic profile; identify the optimal dose, schedule, and MTD; obtain preliminary evidence of activity; and evaluate SRA737's efficacy in prospectively-selected subjects with tumors that harbor genomic alterations linked to increased replication stress and that are hypothesized to be more sensitive to Chk1 inhibition via synthetic lethality.
This clinical study consists of two phases, a Dose Escalation Phase 1 portion and a Cohort Expansion Phase 2 portion.
In the Dose Escalation Phase 1 portion, cohorts consisting initially of a single subject will receive escalating doses of SRA737, administered orally on a continuous daily dosing schedule in 28-day cycles. Once an SRA737-related Grade 2 toxicity is observed in a dose escalation cohort during Cycle 1, that cohort will be expanded to 3 to 6 subjects, and subsequent dose level cohorts will follow a rolling 6 design until the MTD has been identified.
In the Cohort Expansion Phase 2 portion, subjects with genetically-defined tumors that harbor genomic alterations linked to increased replication stress and that are hypothesized to be more sensitive to Chk1 inhibition will be prospectively enrolled into six indication-specific cohorts to explore the preliminary efficacy of SRA737. Subjects must have advanced or metastatic disease of one of the following types:
- castration-resistant prostate cancer (mCRPC);
- high grade serous ovarian cancer (HGSOC) without CCNE1 gene amplification;
- HGSOC with CCNE1 gene amplification (or alternative genetic alteration with similar functional effect);
- non-small cell lung cancer (NSCLC);
- head and neck squamous cell carcinoma (HNSCC) or squamous cell carcinoma of the anus (SCCA); and
- colorectal cancer (mCRC).
To qualify for enrolment in the Cohort Expansion Phase 2 portion, the subject's tumor must have a confirmed combination of mutations which are expected to confer sensitivity to Chk1 inhibition, determined by the Sponsor's review of genetic abnormalities detected in the following categories:
- Oncogenic drivers such as CCNE1 or MYC, etc.
- Genes involved in the DNA repair process including BRCA1, BRCA2, FANC genes, mismatch repair (MMR) genetic alterations and/or high microsatellite instability.
- Key tumor suppressor genes regulating G1 cell cycle progression/arrest such as TP53, RAD50, etc. For patients with HNSCC or SCCA, positive human papilloma virus (HPV) status is also considered for eligibility.
- Genetic indicators of replicative stress such as gain of function/amplification of CHEK1, ATR or other related genes.
Tumor genetics will be prospectively determined using Next-Generation Sequencing.
- Being tested
- SRA737
- Keywords
- Replication stress, Advanced solid tumors, CCNE1, TP53, BRCA1, BRCA2, MYC, RAD50, Fanconi anemia, Cell cycle, Metastatic Colorectal Cancer, Platinum-Resistant or Intolerant High Grade Serious Ovarian Cancer, Advanced Non-Small Cell Lung Cancer, Metastatic Castration-Resistant Prostate Cancer, Head and Neck Squamous Cell Carcinoma, Squamous Cell Carcinoma of the Anus, Phase 1, Phase 2, Dose escalation, Chk1 inhibitor
- Medical subject headings
- Lymphoma, Non-Hodgkin, Fanconi Anemia, Colorectal Neoplasms, Squamous Cell Carcinoma of Head and Neck, Anus Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SRA737Drug
SRA737 will be administered orally on each day of a 28-day cycle. Subjects will receive a single dose of SRA737 between 4 to 7 days prior to starting the first cycle for PK profiling. Subjects can continue taking SRA737 if they are receiving clinical benefit and able to safely take the drug and follow the requirements of the study.
| Study group | Role | What they receive |
|---|---|---|
| Open label | Experimental | Not described Receives: Drug: SRA737 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Adverse Events as Assessed by CTCAE 4.03
Treatment-emergent adverse events (TEAEs) were reported until the safety Follow up (SFU) visit, 30 days after the last dose of SRA737 or prior to the initiation of a new anticancer treatment, whichever came first.
Measured: Up to 30 days after last dose of SRA737
Maximum Tolerated Dose of SRA737
The highest dose at which ≤ 33% of subjects have a dose limiting toxicity (DLT) in a cohort of up to 6 subjects.
Measured: Cycle 1 (28 days) in the Dose Escalation Phase
Recommended Phase 2 Dose of SRA737
The RP2D and schedule were defined by the Cohort Review Committee at the end of the study and took all clinically relevant toxicity, PK and PDn data into account. The RP2D was to be a dose equal to or less than the MTD for the selected schedule.
Measured: Up to 30 days after last dose of SRA737
Disease Control Rate (DCR) of SRA737
The disease control rate (DCR) was defined as the number of subjects achieving complete response (CR) + partial response (PR) + stable disease (SD) per RECIST 1.1 criteria. Since no subjects achieved CR or PR in this study, the DCR represents the proportion of subjects in each group who achieved SD.
Measured: Radiographic tumor assessments were performed every 2 cycles of therapy.
Time to Progression (TTP)
Time to progression (TTP) was defined as the time from Cycle 1 Day 1 to the earliest date of radiographic disease progression per RECIST 1.1, or if the subject did not experience disease progression, to the last imaging assessment. TTP was analyzed using the K-M method.
Measured: Radiographic tumor assessments were performed every 2 cycles of therapy. Follow-up assessments were made every 16 weeks for subjects who had not progressed and had not initiated new anticancer therapy.
Progression Free Survival (PFS)
Progression free survival (PFS) was defined as time from Cycle 1 Day 1 to the earliest date of radiographic disease progression per RECIST 1.1 or death, whichever happened first. Censoring rules are defined in the SAP. PFS was analyzed using the K-M method.
Measured: Radiographic tumor assessments were performed every 2 cycles of therapy. Follow-up assessments were made every 16 weeks for subjects who had not progressed and had not initiated new anticancer therapy.
Overall Survival (OS)
Overall survival (OS) was defined as time from Cycle 1 Day 1 to the date of death (or date last known to be alive). OS was analyzed using the K-M method.
Measured: Follow-up assessments were made every 16 weeks for subjects who had not progressed and had not initiated new anticancer therapy.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2016 (estimated)
- Study startJul 2016
- Primary completion28 Oct 2019
- Study completion28 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid Tumors or Non-Hodgkin's Lymphoma (NHL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sierra Oncology LLC - a GSK company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02797964
- Sponsor's protocol ID
- SRA737-01
- Status last verified
- Jun 2023
- First submitted
- 23 May 2016
- Last updated
- 18 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Kristeleit R, Plummer R, Jones R, Carter L, Blagden S, Sarker D, Arkenau T, Evans TRJ, Danson S, Symeonides SN, Veal GJ, Klencke BJ, Kowalski MM, Banerji U. A Phase 1/2 trial of SRA737 (a Chk1 inhibitor) administered orally in patients with advanced cancer. Br J Cancer. 2023 Jul;129(1):38-45. doi: 10.1038/s41416-023-02279-x. Epub 2023 Apr 29.
PubMed 37120671Jin T, Xu L, Wang P, Hu X, Zhang R, Wu Z, Du W, Kan W, Li K, Wang C, Zhou Y, Li J, Liu T. Discovery and Development of a Potent, Selective, and Orally Bioavailable CHK1 Inhibitor Candidate: 5-((4-((3-Amino-3-methylbutyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)picolinonitrile. J Med Chem. 2021 Oct 28;64(20):15069-15090. doi: 10.1021/acs.jmedchem.1c00994. Epub 2021 Oct 19.
PubMed 34665631
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Trial of SRA737 (a Chk1 Inhibitor) Administered Orally in Subjects With Advanced Cancer
- ClinicalTrials.gov ID
- NCT02797964
- Acronym / sponsor ID
- SRA737-01
- Keywords
- Replication stress, Advanced solid tumors, CCNE1, TP53, BRCA1, BRCA2, MYC, RAD50
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Sierra Oncology LLC - a GSK companyIndustry (pharma, biotech, devices)
- Study start
- Jul 2016 (actual)
- Primary completion
- 28 Oct 2019 (actual)
- Study completion
- 28 Oct 2019 (actual)
- First posted
- 14 Jun 2016 (estimated)
- Results
- Posted 10 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this clinical study is to establish the safety profile, determine the maximum tolerated dose (MTD) and recommend a Phase 2 dose and schedule of SRA737; and to evaluate the efficacy of SRA737 in prospectively-selected subjects with genetically-defined tumors that harbor genomic alterations linked to increased replication stress and that are hypothesized to be more sensitive to checkpoint kinase 1 (Chk1) inhibition via synthetic lethality. Specific cancer indications that frequently harbor these genetic mutations will be studied.
Detailed description
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Chk1, a key regulator of cell cycle progression and the DNA Damage Response (DDR) replication stress response. In cancer cells, intrinsic replication stress (RS) is induced by factors such as oncogenes (e.g., CCNE1 or MYC), genetic mutations in DNA repair machinery (e.g. BRCA1 or FANCA), genetic mutations leading to a dysregulated cell cycle (e.g., TP53 or RAD50) or other genomic alterations. This replication stress results in persistent DNA damage and genomic instability, leading to an increased dependency on Chk1 for survival. Targeted inhibition of Chk1 by SRA737 may therefore be synthetically lethal to cancer cells with elevated intrinsic RS.
This study has been designed to: establish the safety profile; determine the pharmacokinetic profile; identify the optimal dose, schedule, and MTD; obtain preliminary evidence of activity; and evaluate SRA737's efficacy in prospectively-selected subjects with tumors that harbor genomic alterations linked to increased replication stress and that are hypothesized to be more sensitive to Chk1 inhibition via synthetic lethality.
This clinical study consists of two phases, a Dose Escalation Phase 1 portion and a Cohort Expansion Phase 2 portion.
In the Dose Escalation Phase 1 portion, cohorts consisting initially of a single subject will receive escalating doses of SRA737, administered orally on a continuous daily dosing schedule in 28-day cycles. Once an SRA737-related Grade 2 toxicity is observed in a dose escalation cohort during Cycle 1, that cohort will be expanded to 3 to 6 subjects, and subsequent dose level cohorts will follow a rolling 6 design until the MTD has been identified.
In the Cohort Expansion Phase 2 portion, subjects with genetically-defined tumors that harbor genomic alterations linked to increased replication stress and that are hypothesized to be more sensitive to Chk1 inhibition will be prospectively enrolled into six indication-specific cohorts to explore the preliminary efficacy of SRA737. Subjects must have advanced or metastatic disease of one of the following types:
- castration-resistant prostate cancer (mCRPC);
- high grade serous ovarian cancer (HGSOC) without CCNE1 gene amplification;
- HGSOC with CCNE1 gene amplification (or alternative genetic alteration with similar functional effect);
- non-small cell lung cancer (NSCLC);
- head and neck squamous cell carcinoma (HNSCC) or squamous cell carcinoma of the anus (SCCA); and
- colorectal cancer (mCRC).
To qualify for enrolment in the Cohort Expansion Phase 2 portion, the subject's tumor must have a confirmed combination of mutations which are expected to confer sensitivity to Chk1 inhibition, determined by the Sponsor's review of genetic abnormalities detected in the following categories:
- Oncogenic drivers such as CCNE1 or MYC, etc.
- Genes involved in the DNA repair process including BRCA1, BRCA2, FANC genes, mismatch repair (MMR) genetic alterations and/or high microsatellite instability.
- Key tumor suppressor genes regulating G1 cell cycle progression/arrest such as TP53, RAD50, etc. For patients with HNSCC or SCCA, positive human papilloma virus (HPV) status is also considered for eligibility.
- Genetic indicators of replicative stress such as gain of function/amplification of CHEK1, ATR or other related genes.
Tumor genetics will be prospectively determined using Next-Generation Sequencing.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Open label | Experimental | Drug: SRA737 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- For Dose Escalation Only: any locally advanced or metastatic, histologically or cytologically proven solid tumor or NHL, relapsed after or progressing despite conventional treatment
- Life expectancy of at least 12 weeks
- World Health Organization (WHO) performance status of 0-1
- Must meet select hematological and biochemical laboratory indices
- Archival tumor tissue or accessible tumor and willingness to consent to a biopsy
Key exclusion criteria (21 listed)
- Received the following prior or current anticancer therapy:
- Other malignancy within the past 2 years, except for adequately treated tumors
- Ongoing toxic manifestations of previous treatments greater than NCI-CTCAE Grade 1
- For Dose Escalation: new or progressing brain metastases. For Cohort Expansion: present or prior brain metastases
- High medical risk because of nonmalignant systemic disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SRA737SRA737 will be administered orally on each day of a 28-day cycle. Subjects will receive a single dose of SRA737 between 4 to 7 days prior to starting the first cycle for PK profiling. Subjects can continue taking SRA737 if they are receiving clinical benefit and able to safely take the drug and follow the requirements of the study. | Drug | Open label |
Primary outcome
Number of Subjects With Adverse Events as Assessed by CTCAE 4.03
Time frame: Up to 30 days after last dose of SRA737
Treatment-emergent adverse events (TEAEs) were reported until the safety Follow up (SFU) visit, 30 days after the last dose of SRA737 or prior to the initiation of a new anticancer treatment, whichever came first.
Maximum Tolerated Dose of SRA737
Time frame: Cycle 1 (28 days) in the Dose Escalation Phase
The highest dose at which ≤ 33% of subjects have a dose limiting toxicity (DLT) in a cohort of up to 6 subjects.
Recommended Phase 2 Dose of SRA737
Time frame: Up to 30 days after last dose of SRA737
The RP2D and schedule were defined by the Cohort Review Committee at the end of the study and took all clinically relevant toxicity, PK and PDn data into account. The RP2D was to be a dose equal to or less than the MTD for the selected schedule.
Disease Control Rate (DCR) of SRA737
Time frame: Radiographic tumor assessments were performed every 2 cycles of therapy.
The disease control rate (DCR) was defined as the number of subjects achieving complete response (CR) + partial response (PR) + stable disease (SD) per RECIST 1.1 criteria. Since no subjects achieved CR or PR in this study, the DCR represents the proportion of subjects in each group who achieved SD.
Time to Progression (TTP)
Time frame: Radiographic tumor assessments were performed every 2 cycles of therapy. Follow-up assessments were made every 16 weeks for subjects who had not progressed and had not initiated new anticancer therapy.
Time to progression (TTP) was defined as the time from Cycle 1 Day 1 to the earliest date of radiographic disease progression per RECIST 1.1, or if the subject did not experience disease progression, to the last imaging assessment. TTP was analyzed using the K-M method.
Progression Free Survival (PFS)
Time frame: Radiographic tumor assessments were performed every 2 cycles of therapy. Follow-up assessments were made every 16 weeks for subjects who had not progressed and had not initiated new anticancer therapy.
Progression free survival (PFS) was defined as time from Cycle 1 Day 1 to the earliest date of radiographic disease progression per RECIST 1.1 or death, whichever happened first. Censoring rules are defined in the SAP. PFS was analyzed using the K-M method.
Overall Survival (OS)
Time frame: Follow-up assessments were made every 16 weeks for subjects who had not progressed and had not initiated new anticancer therapy.
Overall survival (OS) was defined as time from Cycle 1 Day 1 to the date of death (or date last known to be alive). OS was analyzed using the K-M method.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37120671Kristeleit R, Plummer R, Jones R, Carter L, Blagden S, Sarker D, Arkenau T, Evans TRJ, Danson S, Symeonides SN, Veal GJ, Klencke BJ, Kowalski MM, Banerji U. A Phase 1/2 trial of SRA737 (a Chk1 inhibitor) administered orally in patients with advanced cancer. Br J Cancer. 2023 Jul;129(1):38-45. doi: 10.1038/s41416-023-02279-x. Epub 2023 Apr 29.
- Derived from this study: PubMed 34665631Jin T, Xu L, Wang P, Hu X, Zhang R, Wu Z, Du W, Kan W, Li K, Wang C, Zhou Y, Li J, Liu T. Discovery and Development of a Potent, Selective, and Orally Bioavailable CHK1 Inhibitor Candidate: 5-((4-((3-Amino-3-methylbutyl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)picolinonitrile. J Med Chem. 2021 Oct 28;64(20):15069-15090. doi: 10.1021/acs.jmedchem.1c00994. Epub 2021 Oct 19.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing SRA737 in people with Advanced Solid Tumors or Non-Hodgkin's Lymphoma (NHL), run by Sierra Oncology LLC - a GSK company at 15 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Subjects With Adverse Events as Assessed by CTCAE 4.03 (time frame: Up to 30 days after last dose of SRA737). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02797964, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2023.