NCT01953926: SUMMIT

Basket Study of Neratinib in Participants With Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations

Terminated Phase 2 Results posted Last updated 12 March 2024

What this trial tests

Phase 2 trial testing Neratinib in Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations in 582 participants. Terminated before completion.

Timeline

30 September 2013

Primary endpoint
2 January 2023

2 January 2023

Quick facts

Lead sponsor	Puma Biotechnology, Inc.
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	582
Start date	30 September 2013
Primary completion	2 January 2023
Estimated completion	2 January 2023
Sites	60 locations across Denmark, France, Italy, Belgium, Serbia, Ireland, United Kingdom, Israel

Drugs / interventions tested

• Neratinib — full drug profile →
• Fulvestrant (fulvestrant) — full drug profile →
• Trastuzumab (trastuzumab) — full drug profile →
• Paclitaxel — full drug profile →

Conditions studied

• Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations — all drugs for Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations →

Sponsor

Puma Biotechnology, Inc. — full company profile →

Who can join

18 and older, any sex, with Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Confirmed Objective Response Rate (ORR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort) Primary · From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months

Percentage of participants who are confirmed by independent central review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (HR+, HER2 negative metastatic breast cancer cohorts). Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1) for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Group	Value	95% CI
Breast HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab)	40.7
Breast HR+ w. Prior CDK4/6i (Fulvestrant)	0
Breast HR+ With Prior CDK4/6i (Fulvestrant + Trastuzumab)	14.3

Confirmed Objective Response Rate (ORR) by Investigator Review (Cervical Cancer Cohort) Primary · From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months

Percentage of participants who are confirmed by investigator review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (cervical cancer cohort). Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1) for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Group	Value	95% CI
Cervical (Neratinib)	18.2

Objective Response Rate (ORR) at First Assessment by Investigator Review (All Other Cohorts) Primary · From first treatment date to first Complete or Partial Response, whichever came earlier, assessed up to 8 or 9 weeks

Percentage of participants who achieve CR or PR per Response Evaluation Criteria in Sold Tumors Criteria (RECIST) v1.1, or other defined response criteria, at the first scheduled tumor assessment (all other cohorts), per RECIST (if assessed) or PERCIST. RECISTv1.1 for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR PERCISTv1.0: Complete Metabolic Response - Complete resolution of 18F-FDG uptake within measurable target les

Group	Value	95% CI
Breast Cancer (Neratinib)	36.1
Breast Cancer HR+ (Neratinib + Fulvestrant)	42.2
Breast Cancer HR+ (Neratinib + Fulvestrant + Trastuzumab)	48.4
Breast Cancer HR- (Neratinib + Trastuzumab)	33.3
Lung Cancer HER2 Mutant (Neratinib)	3.8
Lung Cancer HER2 Mutant (Neratinib + Trastuzumab)	15.4
Lung Cancer EGFR Mutant Exon 18 (Neratinib)	19.4
Biliary Tract Cancer (Neratinib)	12.0
Bladder/Urinary Tract Cancer (Neratinib)	0
Bladder/Urinary Tract Cancer (Neratinib + Paclitaxel)	13.6
Brain Cancer (Neratinib)	0
Colorectal Cancer (Neratinib)	0

Confirmed Objective Response Rate (ORR) by Investigator Review (Breast Cancer With Prior CDK46i Cohort) Secondary · From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months

Percentage of participants who are confirmed by investigator review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (HR+, HER2 negative metastatic breast cancer cohorts). Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1) for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Group	Value	95% CI
Breast HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab)	30.5
Breast HR+ w. Prior CDK4/6i (Fulvestrant)	0
Breast HR+ With Prior CDK4/6i (Fulvestrant + Trastuzumab)	0

Confirmed Objective Response Rate (ORR) by Investigator Review (All Other Cohorts) Secondary · From first treatment date to confirmed Complete or Partial Response, assessed up to 58 months.

Percentage of participants who achieve CR or PR per RECIST v1.1, or metabolic complete response via PERCIST v1.0. For RECIST, A complete or partial response that is confirmed no less than 4-weeks after the criteria for response are initially met. PERCIST criteria were used for patients without RECIST assessments.

Group	Value	95% CI
Breast Cancer (Neratinib)	25.0
Breast Cancer HR+ (Neratinib + Fulvestrant)	28.9
Breast Cancer HR+ (Neratinib + Fulvestrant + Trastuzumab)	35.5
Breast Cancer HR- (Neratinib + Trastuzumab)	33.3
Lung Cancer HER2 Mutant (Neratinib)	3.8
Lung Cancer HER2 Mutant (Neratinib + Trastuzumab)	9.6
Lung Cancer EGFR Mutant Exon 18 (Neratinib)	32.3
Biliary Tract Cancer (Neratinib)	16.0
Bladder/Urinary Tract Cancer (Neratinib)	0
Bladder/Urinary Tract Cancer (Neratinib + Paclitaxel)	13.6
Brain Cancer (Neratinib)	2.6
Colorectal Cancer (Neratinib)	0

Duration of Response (DOR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort) Secondary · From first response to first disease progression or death, assessed up to 58 months

Time from which measurement criteria are met for response (whichever status is recorded first) until the first date of documented disease progression or death. Disease progression assessed by RECIST criteria, or for PERCIST for those participants who did not have RECIST performed.

Group	Value	95% CI
Breast Cancer HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab)	13.14	6.41 – NA
Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant + Trastuzumab)	NA	NA – NA

Duration of Response (DOR) by Investigator Review (All Cohorts) Secondary · From first response to first disease progression or death, assessed up to 58 months

Time from which measurement criteria are met for response (whichever status is recorded first) until the first date of documented disease progression or death. Disease progression assessed by RECIST criteria, or for PERCIST for those participants who did not have RECIST performed.

Group	Value	95% CI
Breast Cancer HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab)	14.4	7.8 – 18.6
Breast Cancer (Neratinib)	4.76	3.71 – 16.62
Breast Cancer HR+ (Neratinib + Fulvestrant)	9.23	5.49 – 38.97
Breast Cancer HR+ (Neratinib + Fulvestrant + Trastuzumab)	9.17	4.14 – NA
Breast Cancer HR- (Neratinib + Trastuzumab)	7.28	4.17 – NA
Cervical Cancer (Neratinib)	7.62	5.55 – 12.25
Lung Cancer HER2 Mutant (Neratinib)	9.23	NA – NA
Lung Cancer HER2 Mutant (Neratinib + Trastuzumab)	6.80	4.17 – NA
Lung Cancer EGFR Mutant Exon 18 (Neratinib)	22.24	4.01 – 30.03
Biliary Tract Cancer (Neratinib)	3.75	2.99 – 4.67
Bladder/Urinary Tract Cancer (Neratinib + Paclitaxel)	7.20	2.76 – 7.59
Brain Cancer (Neratinib)	19.94	NA – NA

Clinical Benefit Rate (CBR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort) Secondary · From enrollment date to first documented response or stable disease ≥16, or ≥24 weeks for breast cancer, assessed up to 58 months

Percentage of participants with CR + PR + stable disease ≥16, or ≥24 weeks for breast cancer, from the date of enrollment.

Group	Value	95% CI
Breast Cancer HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab)	49.2
Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant)	0
Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant + Trastuzumab)	14.3

Clinical Benefit Rate (CBR) by Investigator Review (All Cohorts) Secondary · From enrollment date to first documented response or stable disease ≥16, or ≥24 weeks for breast cancer, assessed up to 58 months

Percentage of participants with CR + PR + stable disease ≥16, or ≥24 weeks for breast cancer, from the date of enrollment.

Group	Value	95% CI
Breast Cancer HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab)	54.2
Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant)	0
Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant + Trastuzumab)	0
Breast Cancer (Neratinib)	33.3
Breast Cancer HR+ (Neratinib + Fulvestrant)	42.2
Breast Cancer HR+ (Neratinib + Fulvestrant + Trastuzumab)	54.8
Breast Cancer HR- (Neratinib + Trastuzumab)	42.9
Cervical Cancer (Neratinib)	45.5
Lung Cancer HER2 Mutant (Neratinib)	38.5
Lung Cancer HER2 Mutant (Neratinib + Trastuzumab)	30.8
Lung Cancer EGFR Mutant Exon 18 (Neratinib)	48.4
Biliary Tract Cancer (Neratinib)	24.0

Progression-Free Survival (PFS) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort) Secondary · From enrollment date until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to 58 months

Number of months between first dose date and the first date on which recurrence, progression, or death due to any cause, is documented, censored at the last tumor assessment or at the initiation of new anticancer therapy. Progression was defined by RECIST criteria for those participants with RECIST assessments; and PERCIST criteria for other participants.

Group	Value	95% CI
Breast Cancer HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab)	8.11	6.01 – 16.39
Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant)	2.27	1.61 – NA
Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant + Trastuzumab)	4.11	1.87 – 4.11

Progression-Free Survival (PFS) by Investigator Review (All Cohorts) Secondary · From enrollment date until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to 58 months

Number of months between first dose date and the first date on which recurrence, progression, or death due to any cause, is documented, censored at the last tumor assessment or at the initiation of new anticancer therapy. Progression was defined by RECIST criteria for those participants with RECIST assessments; and PERCIST criteria for other participants.

Group	Value	95% CI
Breast Cancer HR+ w Prior CDK4/6i (Neratinib + Fulvestrant + Trastuzumab)	8.3	6.0 – 12.7
Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant)	4.1	1.6 – 4.1
Breast Cancer HR+ w Prior CDK4/6i (Fulvestrant + Trastuzumab)	3.9	1.9 – 4.1
Breast Cancer (Neratinib)	3.48	1.94 – 3.88
Breast Cancer HR+ (Neratinib + Fulvestrant)	5.36	3.71 – 9.23
Breast Cancer HR+ (Neratinib + Fulvestrant + Trastuzumab)	8.21	4.07 – 11.01
Breast Cancer HR- (Neratinib + Trastuzumab)	6.24	2.10 – 10.25
Cervical Cancer (Neratinib)	5.09	1.74 – 7.23
Lung Cancer HER2 Mutant (Neratinib)	4.17	1.87 – 8.80
Lung Cancer HER2 Mutant (Neratinib + Trastuzumab)	4.01	2.10 – 4.57
Lung Cancer EGFR Mutant Exon 18 (Neratinib)	5.75	2.27 – 9.23
Biliary Tract Cancer (Neratinib)	2.76	1.05 – 3.75

Number of Participants With Treatment-Emergent Adverse Events Secondary · From first dose through 28 days after the last dose, assessed up to 75 months.

The safety of neratinib in patients as measured by the incidence of treatment-emergent adverse events (TEAE), including serious adverse events (SAEs), in study participants. TEAEs are any adverse event that occurred on or after first dose of investigational product and up to 28 days after the last dose

Any treatment-emergent adverse event

Group	Value	95% CI
Neratinib	313
Neratinib + Fulvestrant	45
Neratinib + Paclitaxel	21
Neratinib + Trastuzumab	92
Neratinib + Fulvestrant + Trastuzumab	89
Fulvestrant	7
Fulvestrant + Trastuzumab	7

Any treatment-emergent serious adverse event

Group	Value	95% CI
Neratinib	144
Neratinib + Fulvestrant	12
Neratinib + Paclitaxel	13
Neratinib + Trastuzumab	45
Neratinib + Fulvestrant + Trastuzumab	28
Fulvestrant	5
Fulvestrant + Trastuzumab	0

Adverse events — posted to ClinicalTrials.gov

Time frame: All events from day 1 of study drug through 28 days after last dose are included, up to 75 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Neratinib

Serious: 144/317 (45%)

Deaths: 231/317

Neratinib + Fulvestrant

Serious: 12/45 (27%)

Deaths: 31/45

Neratinib + Paclitaxel

Serious: 13/22 (59%)

Deaths: 14/22

Neratinib + Trastuzumab

Serious: 45/92 (49%)

Deaths: 71/92

Neratinib + Fulvestrant + Trastuzumab

Serious: 28/90 (31%)

Deaths: 32/90

Fulvestrant

Serious: 5/7 (71%)

Deaths: 2/7

Fulvestrant + Trastuzumab

Serious: 0/7 (0%)

Deaths: 0/7

Serious adverse events (172 terms)

Reaction	System	Neratinib	Neratinib + Fulvestrant	Neratinib + Paclitaxel	Neratinib + Trastuzumab	Neratinib + Fulvestrant + …	Fulvestrant	Fulvestrant + Trastuzumab
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—
Sepsis	Infections and infestations	—	—	—	—	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—	—	—	—	—
Ascites	Gastrointestinal disorders	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Atrial fibrillation	Cardiac disorders	—	—	—	—	—	—	—
Large intestinal obstruction	Gastrointestinal disorders	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—
General physical health deterioration	General disorders	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Brain oedema	Nervous system disorders	—	—	—	—	—	—	—

Other adverse events (108 terms — click to expand)

Reaction	System	Neratinib	Neratinib + Fulvestrant	Neratinib + Paclitaxel	Neratinib + Trastuzumab	Neratinib + Fulvestrant + …	Fulvestrant	Fulvestrant + Trastuzumab
Diarrhoea	Gastrointestinal disorders	—	—	—	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—	—	—	—
Fatigue	General disorders	—	—	—	—	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—	—	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—	—	—	—	—
Weight decreased	Investigations	—	—	—	—	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—	—	—	—	—
Headache	Nervous system disorders	—	—	—	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Pyrexia	General disorders	—	—	—	—	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—	—	—	—	—
Asthenia	General disorders	—	—	—	—	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Oedema peripheral	General disorders	—	—	—	—	—	—	—
Urinary tract infection	Infections and infestations	—	—	—	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Blood alkaline phosphatase increased	Investigations	—	—	—	—	—	—	—
Hypertension	Vascular disorders	—	—	—	—	—	—	—
Dysgeusia	Nervous system disorders	—	—	—	—	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—	—	—	—	—
Dry mouth	Gastrointestinal disorders	—	—	—	—	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—	—	—	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—	—	—	—	—
Blood creatinine increased	Investigations	—	—	—	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—	—	—	—
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	—	—	—	—	—	—	—
Insomnia	Psychiatric disorders	—	—	—	—	—	—	—
Hypomagnesaemia	Metabolism and nutrition disorders	—	—	—	—	—	—	—

Most-reported serious reactions: Diarrhoea, Abdominal pain, Vomiting, Dehydration, Nausea, Urinary tract infection, Dyspnoea, Pyrexia.

Data from ClinicalTrials.gov NCT01953926 adverse events section.

Sponsor's own description

This is an open-label, multicenter, multinational, Phase 2 basket study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in participants with HER (EGFR, HER2) mutation-positive solid tumors.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease.
   Bianchini G, Balko JM, Mayer IA, Sanders ME, et al · · 2016 · cited 2163× · PMID 27184417 · DOI 10.1038/nrclinonc.2016.66
2. OncoKB: A Precision Oncology Knowledge Base.
   Chakravarty D, Gao J, Phillips SM, Kundra R, et al · · 2017 · cited 1944× · PMID 28890946 · DOI 10.1200/po.17.00011
3. Targeting HER2-positive breast cancer: advances and future directions.
   Swain SM, Shastry M, Hamilton E. · · 2023 · cited 703× · PMID 36344672 · DOI 10.1038/s41573-022-00579-0
4. HER kinase inhibition in patients with HER2- and HER3-mutant cancers.
   Hyman DM, Piha-Paul SA, Won H, Rodon J, et al · · 2018 · cited 616× · PMID 29420467 · DOI 10.1038/nature25475
5. Implementing Genome-Driven Oncology.
   Hyman DM, Taylor BS, Baselga J. · · 2017 · cited 353× · PMID 28187282 · DOI 10.1016/j.cell.2016.12.015
6. Broad, Hybrid Capture-Based Next-Generation Sequencing Identifies Actionable Genomic Alterations in Lung Adenocarcinomas Otherwise Negative for Such Alterations by Other Genomic Testing Approaches.
   Drilon A, Wang L, Arcila ME, Balasubramanian S, et al · · 2015 · cited 228× · PMID 25567908 · DOI 10.1158/1078-0432.ccr-14-2683
7. Signaling Pathways in Cancer: Therapeutic Targets, Combinatorial Treatments, and New Developments.
   Yip HYK, Papa A. · · 2021 · cited 167× · PMID 33809714 · DOI 10.3390/cells10030659
8. Neratinib Efficacy and Circulating Tumor DNA Detection of <i>HER2</i> Mutations in <i>HER2</i> Nonamplified Metastatic Breast Cancer.
   Ma CX, Bose R, Gao F, Freedman RA, et al · · 2017 · cited 158× · PMID 28679771 · DOI 10.1158/1078-0432.ccr-17-0900