Brief Summary
This study will evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy in human epidermal growth factor receptor (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease has progressed on endocrine therapy in the metastatic setting.
Brief Title
Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer
Detailed Description
Eligible patients will be those patients who have had disease progression on at least 2 previous lines of endocrine therapies given for the treatment of metastatic disease or disease progression within 6 months of starting first line treatment for metastatic disease with an endocrine therapy combined with a CDK4/6 inhibitor. All patients must have historically confirmed HR positive (either estrogen receptor and/or progesterone receptor positive), HER2-low (defined as IHC2+/ISH- and IHC 1+) or HER2 IHC \>0 \<1+ expression, as determined by central laboratory testing results, advanced or metastatic breast cancer.
The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy. This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.
The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy. This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.
Completion Date
Completion Date Type
Estimated
Conditions
Advanced or Metastatic Breast Cancer
Eligibility Criteria
Key Inclusion Criteria:
* Patients must be ≥18 years of age
* Pathologically documented breast cancer that:
1. is advanced or metastatic
2. has a history of HER2-low or negative expression by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested)
3. has HER2-low or HER2 IHC \>0 \<1+ expression as determined by the central laboratory result established on a tissue sample taken in the metastatic setting
4. was never previously HER2-positive
5. is documented HR+ disease in the metastatic setting.
* No prior chemotherapy for advanced or metastatic breast cancer.
* Has adequate tumor samples for assessment of HER2 status
* Must have either:
1. disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or
2. disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting. Of note with regards to the ≥2 lines of previous ET requirement: disease recurrence while on the first 24 months of starting adjuvant ET, will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting.
* Has protocol-defined adequate organ and bone marrow function
Key Exclusion Criteria:
* Ineligible for all options in the investigator's choice chemotherapy arm
* Lung-specific intercurrent clinically significant illnesses
* Uncontrolled or significant cardiovascular disease or infection
* Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current ILD/ pneumonitis, or suspected ILD/ pneumonitis that cannot be ruled out by imaging at screening.
* Patients with spinal cord compression or clinically active central nervous system metastases
* Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
* Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)
* Patients must be ≥18 years of age
* Pathologically documented breast cancer that:
1. is advanced or metastatic
2. has a history of HER2-low or negative expression by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested)
3. has HER2-low or HER2 IHC \>0 \<1+ expression as determined by the central laboratory result established on a tissue sample taken in the metastatic setting
4. was never previously HER2-positive
5. is documented HR+ disease in the metastatic setting.
* No prior chemotherapy for advanced or metastatic breast cancer.
* Has adequate tumor samples for assessment of HER2 status
* Must have either:
1. disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or
2. disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting. Of note with regards to the ≥2 lines of previous ET requirement: disease recurrence while on the first 24 months of starting adjuvant ET, will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting.
* Has protocol-defined adequate organ and bone marrow function
Key Exclusion Criteria:
* Ineligible for all options in the investigator's choice chemotherapy arm
* Lung-specific intercurrent clinically significant illnesses
* Uncontrolled or significant cardiovascular disease or infection
* Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current ILD/ pneumonitis, or suspected ILD/ pneumonitis that cannot be ruled out by imaging at screening.
* Patients with spinal cord compression or clinically active central nervous system metastases
* Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
* Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)
Inclusion Criteria
Inclusion Criteria:
* Patients must be ≥18 years of age
* Pathologically documented breast cancer that:
1. is advanced or metastatic
2. has a history of HER2-low or negative expression by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested)
3. has HER2-low or HER2 IHC \>0 \<1+ expression as determined by the central laboratory result established on a tissue sample taken in the metastatic setting
4. was never previously HER2-positive
5. is documented HR+ disease in the metastatic setting.
* No prior chemotherapy for advanced or metastatic breast cancer.
* Has adequate tumor samples for assessment of HER2 status
* Must have either:
1. disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or
2. disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting. Of note with regards to the ≥2 lines of previous ET requirement: disease recurrence while on the first 24 months of starting adjuvant ET, will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting.
* Has protocol-defined adequate organ and bone marrow function
* Patients must be ≥18 years of age
* Pathologically documented breast cancer that:
1. is advanced or metastatic
2. has a history of HER2-low or negative expression by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested)
3. has HER2-low or HER2 IHC \>0 \<1+ expression as determined by the central laboratory result established on a tissue sample taken in the metastatic setting
4. was never previously HER2-positive
5. is documented HR+ disease in the metastatic setting.
* No prior chemotherapy for advanced or metastatic breast cancer.
* Has adequate tumor samples for assessment of HER2 status
* Must have either:
1. disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or
2. disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting. Of note with regards to the ≥2 lines of previous ET requirement: disease recurrence while on the first 24 months of starting adjuvant ET, will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting.
* Has protocol-defined adequate organ and bone marrow function
Gender
All
Gender Based
false
Keywords
Breast Cancer
HR positive
HER2-Low
HER2-Negative
Trastuzumab Deruxtecan (T-DXd; DS-8201a)
Anti-HER2-Antibody Drug Conjugate (ADC)
DESTINY-Breast06
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
105 Years
Minimum Age
18 Years
NCT Id
NCT04494425
Org Class
Industry
Org Full Name
AstraZeneca
Org Study Id
D9670C00001
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 3, Randomized, Multi-center, Open-label Study of Trastuzumab Deruxtecan (T-DXd) Versus Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Breast Cancer Patients Whose Disease Has Progressed on Endocrine Therapy in the Metastatic Setting (DESTINY-Breast06)
Primary Outcomes
Outcome Description
PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by BICR was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions (TLs), taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 millimeter (mm) from nadir. Median PFS was calculated using Kaplan-Meier method and its confidence interval (CI) using Brookmeyer-Crowley method.
Outcome Measure
Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Low Population
Outcome Time Frame
Response evaluations performed at screening, every 6 weeks (q6w) ± 1 week from randomization for 48 weeks, and then every 9 weeks (q9w) ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Secondary Ids
Secondary Id
2023-505554-18-00
Secondary Id
2019-004493-26
Secondary Outcomes
Outcome Description
OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Median OS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
Outcome Time Frame
From date of randomization until death due to any cause, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Outcome Measure
Overall Survival (OS) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population
Outcome Description
PFS per RECIST 1.1 assessed by BICR was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median PFS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
Outcome Time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Outcome Measure
Progression-Free Survival Assessed by Blinded Independent Central Review in the Intent-to-Treat, Human Epidermal Growth Factor Receptor 2 Immunohistochemistry (IHC) >0 <1+ and Human Epidermal Growth Factor Receptor 2-low Population
Outcome Description
OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Median OS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
Outcome Time Frame
From date of randomization until death due to any cause, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Outcome Measure
Overall Survival (OS) in the Intent-to-Treat Population
Outcome Description
PFS per RECIST 1.1 assessed by Investigator was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median PFS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
Outcome Time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Outcome Measure
Progression-Free Survival Assessed by Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population
Outcome Description
ORR per RECIST 1.1 assessed by BICR and Investigator was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR). CR was defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \<10 mm. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
Outcome Time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Outcome Measure
Objective Response Rate (ORR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population
Outcome Description
DOR per RECIST v1.1 was defined as the time from the date of first documented response until date of documented progression or death in the absence of PD. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median DOR was calculated using Kaplan-Meier method.
Outcome Time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Outcome Measure
Duration of Response (DOR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population
Outcome Description
ORR per RECIST 1.1 assessed by BICR and Investigator was defined as the percentage of participants with at least 1 visit response of CR or PR. CR was defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \<10 mm. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
Outcome Time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Outcome Measure
Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population
Outcome Description
DOR per RECIST v1.1 was defined as the time from the date of first documented response until date of documented progression or death in the absence of PD. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median DOR was calculated using Kaplan-Meier method.
Outcome Time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Outcome Measure
Duration of Response Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat Population
Outcome Description
PFS2 was defined as time from randomization to second progression (the earliest of the progression event subsequent to first subsequent therapy) or death; second progression was defined according to local standard clinical practice and might involve any of the following: objective radiological imaging, symptomatic progression, or death. Median PFS2 was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
Outcome Time Frame
Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Outcome Measure
Time From Randomization to Second Progression or Death (PFS2) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population
Outcome Description
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant administered a medicinal product and which did not necessarily had a causal relationship with this treatment. A serious adverse event (SAE) was an AE occurring during any study phase, that fulfilled 1 or more of following criteria: resulted in death, was immediately life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was congenital abnormality or birth defect, and was an important medical event that jeopardized participant or required medical treatment to prevent 1 of outcomes listed above. TEAE was any AE that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after initiation of the study drug until the 40-day (+7 days) safety follow-up visit.
Outcome Time Frame
From first dose of study drug (Day 1) up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Outcome Measure
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
Outcome Description
Blood samples were collected at indicated time points to determine the concentration of T-DXd, total anti-HER2 antibody and MAAA-1181a in serum.
Outcome Time Frame
Pre-dose on Day 1 of Cycles 1, 2, 4, 6 and 8; 15 minutes post-dose on Day 1 of Cycles 1, 2 and 4; and 5 hours post-dose on Day 1 of Cycle 1 (each cycle is 21 days)
Outcome Measure
Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a
Outcome Description
EORTC QLQ-C30 is a 30-item self-administered questionnaire grouped into 5 multi-item functional scales(physical,role,emotional,cognitive and social),3 multiitem symptom scales(fatigue,pain and nausea/vomiting),2-item global QoL scale,5 single items assessing additional symptoms reported by cancer participants(dyspnea,loss of appetite,insomnia,constipation and diarrhea). All but 2 questions have 4-point scales:1:not at all,2:a little,3:quite a bit,4:very much.2 questions concerning global health status and QoL have 7-point scales with responses ranging from 1:very poor to 7:excellent;higher score:better level of functioning/greater degree of symptoms.For each of 15 scales,final scores were averaged from scores of component items,transformed,range: 0 to 100;higher scores:better functioning,better health related (HR)QoL,or greater level of symptoms(higher scores:opposite interpretations for functioning/QoL and symptoms/problems).Baseline:last observed measurement prior to randomization.
Outcome Time Frame
Baseline (Day 1) and Week 91
Outcome Measure
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91
Outcome Description
EORTC QLQ-BR45 is an updated version of the BR23. Self-administered instrument includes original 23-items yielding 5 multi-item scores (body image, sexual functioning, arm symptoms, breast symptoms, and systemic therapy side effects). Additional 22 items yield 4 additional multi-item scales (breast satisfaction, endocrine therapy symptoms, skin mucosis symptoms, and endocrine sexual symptoms). Single items assess sexual enjoyment, future perspective and being upset by hair loss. Items are scored on a 4-point verbal rating scale: 1: not at all, 2: a little, 3: quite a bit, and 4: very much; higher score: better level of functioning or greater degree of symptoms. Scores of these scales were averaged from scores of component items, transformed, and ranged from 0 to 100; higher scores for functioning scales or items indicate better functioning, whereas higher scores for symptom scales or items represent a higher level of symptoms. Baseline:last observed measurement prior to randomization.
Outcome Time Frame
Baseline (Day 1) and Week 58
Outcome Measure
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58
Outcome Description
Time to deterioration was defined as the time from randomization until the date of the first clinically meaningful deterioration that was confirmed at next available assessment, at least 14 days apart, regardless of whether the participant withdrew from study treatment or receives another anti-cancer therapy prior to deterioration.
Outcome Time Frame
From randomization until date of first symptom deterioration that is confirmed, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Outcome Measure
Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score
Outcome Description
Blood samples were collected at indicated timepoints to determine ADA. Treatment-induced ADA was defined as ADA positive post-baseline and not detected at baseline (negative or missing). Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher-level following drug administration.
Outcome Time Frame
From Day 1 up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Outcome Measure
Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab Deruxtecan
Outcome Description
TFST was defined as time from randomization to the start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment or death due to any cause.
Outcome Time Frame
From Day 1 up to 64 months
Outcome Measure
Time to First Subsequent Treatment or Death (TFST) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population
Outcome Description
TSST was defined as time from randomization to the start date of the second subsequent anti-cancer therapy after discontinuation of randomized treatment or death due to any cause.
Outcome Time Frame
From Day 1 up to 64 months
Outcome Measure
Time to Second Subsequent Treatment or Death (TSST) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
105
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sun Young Oh
Investigator Email
suyoung@montefiore.org
Investigator Phone
918-405-8404
Categories Mesh Debug
Breast Cancer --- BREAST NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Breast Cancer --- BREAST DISEASES
Gastrointestinal (GI) Cancers --- CAPECITABINE
MeSH Terms
BREAST NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
BREAST DISEASES
SKIN DISEASES
SKIN AND CONNECTIVE TISSUE DISEASES
TRASTUZUMAB DERUXTECAN
CAPECITABINE
PACLITAXEL
130-NM ALBUMIN-BOUND PACLITAXEL
DEOXYCYTIDINE
CYTIDINE
PYRIMIDINE NUCLEOSIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
FLUOROURACIL
URACIL
PYRIMIDINONES
DEOXYRIBONUCLEOSIDES
NUCLEOSIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
ORGANIC CHEMICALS
DITERPENES
TERPENES