Oncology Regulatory Review
Highlights of 2021
The OCE collaborates with the three FDA product centers reviewing drugs, biologic therapies, and devices to develop and execute an integrated regulatory approach to enhance the cross-center coordination of oncology product clinical review.
The Office of Oncologic Diseases (OOD) in the Center for Drug Evaluation and Research (CDER) approved four new drugs for non-small lung cancer (Tepmetko, Rybrevant, Lumakras, Exkivity), including one non-small cell lung cancer type previously thought to be resistant to treatment.
For skin cancer, OOD approved a therapy (Libtayo) for some types of basal cell carcinoma, the most common form of `skin cancer, for certain patient populations.
OOD also approved the first immunotherapy (Opdivo), or therapy that stimulates or suppresses the immune system, as a first-line treatment for esophageal (esophagus-related) cancer, gastric (stomach) cancer, and gastroesophageal junction (GEJ) adenocarcinoma, a rare cancer that starts where the esophagus and stomach join together. Also related to stomach and esophageal cancer, OOD approved two other therapies (Enhertu and Keytruda) for certain patients with HER2-positive gastric cancer and GEJ adenocarcinoma, one of which (Keytruda) also was approved for esophageal cancer, advanced kidney cancer, and as an add-on treatment for kidney cancer.
Additionally, OOD approved Keytruda for early-stage, triple negative breast cancer, or cancer that does not respond to hormonal therapies or medications that target HER2 protein receptors.
Other approvals for rare cancers included:
- Two treatments (Truseltiq and Tibsovo) for adults with certain kinds of cholangiocarcinoma, a group of aggressive cancers that start in the bile duct.
- A therapy (Welireg) for use in adults to treat certain tumors that are associated with von Hippel-Lindau disease an inherited disorder characterized by tumors and cysts.
- A therapy (Darzalex Faspro) to be used together with other treatments for light chain amyloidosis, a cancer occurring when an abnormal protein builds up in the organs.
- A treatment (Fyarro) for locally advanced unresectable or metastatic perivascular epithelioid cell tumor (PEComa), a group of rare tumors that form in the soft tissues of the stomach, intestines, lungs and other body parts. This is the first FDA-approved treatment for PEComa.
The Center for Biologics Evaluation and Research (CBER) reviews and regulates cellular cancer therapies in partnership with OCE.
In 2021, CBER and OCE approved a new biologic therapy, Abecma (idecabtagene vicleucel) for adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
Also, a new indication was granted for Tecartus (brexucabtagene autoleucel) for treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Tecartus was previously approved for treatment of adults with relapsed or refractory mantle cell lymphoma.
In addition, FDA granted accelerated approval to Yescarta (axicabtagene ciloleucel) for adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.
Visit Oncology (Cancer) / Hematologic Malignancies Approval Notifications for further information on drug and biologics approvals.
The Center for Devices and Radiological Health (CDRH) reviews and regulates oncology devices and diagnostics in partnership with OCE. During 2021, CDRH and OCE authorized 16 oncology-related in vitro diagnostic devices (IVDs) including 12 companion diagnostic approvals.
Eight companion diagnostic devices were approved in areas of unmet need such as for the treatment of cholangiocarcinoma and to detect KRAS G12C variants in patients with non-small cell lung cancer. The first tumor agnostic immunohistochemistry companion diagnostic was authorized for the identification of patients with solid tumors that are DNA mismatch repair deficient. In addition, a second group labeling claim was approved, for patients with unresectable or metastatic melanoma to detect specific BRAF variants for the selection of BRAF inhibitors or BRAF/MEK inhibitor combinations.
Visit Oncology Therapeutic and Diagnostic Devices for further information on device approvals.
2021 Oncology Approvals*
|NMEs/ Original BLA||16 (6 Regular, 12 AA)** (9 RTOR) (6 AAid)|
|Supplements (new indication)||50 (43 Regular, 7 AA) (16 RTOR) (26 AAid)|
|Supplements (new population)||8|
|In vitro diagnostic devices (PMAs)||16 (12 companion diagnostics)|
|Breakthrough Designation||25 (22 CDER, 3 CBER)|
|Breakthrough Device Designation||13|
|Priority Review||70 (68 CDER, 2 CBER)|
*Approval numbers reflect approvals from CBER, CDER and CDRH
** The number of regular and accelerated approvals is greater than the total number of NMEs because some NME applications are administratively split due to different actions for different indications within the NME.
AA: Accelerated Approval; AAid: Assessment Aid; BLA: Biologics License Application; NME: new molecular entity; PMA: Premarket Approval; RTOR: Real-Time Oncology Review.
OCE’s Project Orbis provides a framework for concurrent submission and review of oncology products among international partners. FDA approved the following drug-indication combinations through Project Orbis in 2021. Click on the links in the date to read about each approval.
Project Orbis Drug Approvals
|Approval Date||Product Name(s)||Indication||AAid/RTOR|
|1.||1/15/2021||Enhertu 5 (fam-trastuzumab
|2.||1/15/2021||Darzalex Faspro 1
(daratumumab and hyaluronidase-fihj)
|3.||2/3/2021||Tepmetko (tepotinib 1,2)||MET exon 14
|4.||3/3/2021||Lobrena (lorlatinib 4)||1L ALK+ NSCLC||Y/Y|
|9.||5/20/2021||Opdivo (nivolumab)||GEJ (adjuvant)||Y/Y|
EGFR exon 20 insertion mutations
|11.||5/28/2021||Truseltiq (infigratinib 1,2)||cholangiocarcinoma||Y/Y|
|12.||5/28/2021||Lumakras (sotorasib 1,2)||NSCLC, KRAS G12C mutated||Y/Y|
|13.||6/30/2021||Rylaze (asparaginase erwinia chrysanthemi
|ALL & LBL||Y/Y|
|15.||7/16/2021||Rezurock (belumosudil 2)||cGvHD||Y/Y|
Lenvima 3,4,5 (lenvatinib)
|Advanced EC not MSI-H or dMMR||Y/N|
|17.||7/26/2021||Keytruda 3,4,5 (pembrolizumab)||TNBC||Y/Y|
|18.||8/13/2021||Welireg 2(belzutifan)||VHL disease
|19.||9/15/2021||Exkivity 1,2 (mobocertinib)||NSCLC,
EGFR exon 20 insertion mutations
Node+, HR+, HER2-
|22.||10/13/2021||Keytruda 3,4 (pembrolizumab)||cervical cancer, tumors express PD-L1 (CPS ≥ 1)||Y/N|
|23.||10/15/2021||Tecentriq (atezolizumab)||adjuvant NSCLC, stage II to IIIA||Y/Y|
|24.||11/17/2021||Keytruda (pembrolizumab)||adjuvant RCC||Y/N|
|25.||12/3/2021||Keytruda 5 (pembrolizumab)||adjuvant melanoma||Y/Y|
|26.||12/15/2021||Orencia (abatacept)||aGVHD prophylaxis||Y/N|
1 Accelerated Approval (AA)
2 New Molecular Entity (NME) or new biologic
3 Two separate applications associated with approval.
4 Convert AA
5 Type C Orbis – share unredacted FDA reviews, minimal collaboration if any
The OCE Pediatric Oncology Program facilitates early pediatric studies of appropriate new, targeted cancer therapeutics to eliminate long lag times between first-in-human and first-in-children studies of approved cancer drugs. To do this, we attempt to maximize the authority available through the Best Pharmaceuticals for Children Act to increase the number of Written Requests for pediatric studies of appropriate new drugs developed for adult cancers much earlier in the development timeline.
|Approval Date||Product Name||Indication|
|1.||1/14/2021||Xalkori (crizotinib)||For pediatric patients ≥1 year and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma that is ALK-positive|
|2.||6/30/2021||Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn)||As a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma in adult and pediatric patients ≥1 month who have developed hypersensitivity to E. coli-derived asparaginase|
|3.||7/16/2021||Rezurock (belumosudil)||For adult and pediatric patients ≥12 years with chronic graft-versus-host disease after failure of at least two prior lines of systemic therapy|
|4.||9/17/2021||Cabometyx (cabozantinib)||For adult and pediatric patients ≥12 years and older with locally advanced or metastatic differentiated thyroid cancer that has progressed following prior VEGFR-targeted therapy and who are ineligible or refractory to radioactive iodine|
|5.||9/22/2021||Jakafi (ruxolitinib)||For chronic graft-versus-host disease after failure of one or two lines of systemic therapy in adult and pediatric patients ≥12 years|
|6.||12/2/2021||Rituxan (rituximab)||In combination with chemotherapy for pediatric patients (≥6 months to <18 years) with previously untreated, advanced stage, CD20-positive diffuse large B-cell lymphoma, Burkitt lymphoma, Burkitt-like lymphoma, or mature B-cell acute leukemia|
|7.||12/3/2021||Keytruda (pembrolizumab)||For the adjuvant treatment of adult and pediatric (≥12 years) patients with stage IIB or IIC melanoma following complete resection|
|8.||12/15/2021||Orencia (abatacept)||For the prophylaxis of acute graft versus host disease in combination with a calcineurin inhibitor and methotrexate in adults and pediatric patients (≥2 years) undergoing hematopoietic stem cell transplantation from a matched or 1 allele-mismatched unrelated donor|
Pediatric Oncology Program Reviews in 2021
|Initial Pediatric Study Plans (iPSPs)||297|
|Amended Agreed iPSPs||37|
|Inadequate Proposed Pediatric Study Requests||37|
|Written Requests (WRs)||7|
|Type F Meetings||12|
iPSP: initial Pediatric Study Plan; PPSRs: Proposed Pediatric Study Requests; WRs: Written Requests
The OCE led or participated in the development of eight oncology-specific guidance documents in 2021. The OCE continued efforts to encourage expansion of eligibility criteria and stress enrollment of a diverse population to ensure that clinical trial results are applicable to the US population. FDA finalized a guidance regarding evaluation of patients with CNS metastases and issued a draft Guidance regarding prior therapies that may allow more patients to enroll on trials rather than always having to receive all approved therapies first. See all current oncology guidance documents at OCE Guidances.
- Pharmacokinetic-Based Criteria for Supporting Alternative Dosing Regimens of Programmed Cell Death Receptor-1 (PD-1) or Programmed Cell Death-Ligand 1 (PD-L1) Blocking Antibodies for Treatment of Patients with Cancer (Draft)
- Evaluating Cancer Drugs in Patients with Central Nervous System Metastases (Final)
- Cancer Clinical Trial Eligibility Criteria: Available Therapy in Non-Curative Settings (Draft)
- Premenopausal Women with Breast Cancer: Developing Drugs for Treatment (Final)
- Core Patient-Reported Outcomes in Cancer Clinical Trials (Draft)
- Chemotherapy-Induced Nausea and Vomiting: Developing Drugs for Prevention (Draft)
- COVID-19: Master Protocols Evaluating Drugs and Biological Products for Treatment or Prevention (Final)
- FDARA Implementation Guidance for Pediatric Studies of Molecularly Targeted Oncology Drugs: Amendments to Sec. 505B of the FD&C Act (Final)
Consistent with OCE’s mission to achieve patient-centered regulatory decision making, the OCE PFDD program continued to advance efforts to integrate rigorous measurement of symptoms, function and other patient experience data in cancer trials. In 2021, the program expanded its consult service, providing consistent trial design and regulatory review advice on clinical outcome assessments for over 100 oncology products across review divisions in CDER, CBER and CDRH.
Other highlights included finalizing the first OCE funded prospective clinical study to quantify physical function in collaboration with Yale and Mayo Clinic, release of an OCE draft guidance for industry on core patient-reported outcomes and completion of the sixth annual Clinical Outcomes Assessment in Cancer Clinical Trials workshop.
Select Recent Publications by the OCE PFDD Program:
- Clinical Advances in Hematology & Oncology (2021) “The FDA’s Patient-Focused Drug Development Initiative”
- Blood Cancer Journal (2021) “Review of patient-reported outcomes in multiple myeloma registrational trials: highlighting areas for improvement”
- Journal of the National Cancer Institute (2022) Patient-Reported Outcomes in Pediatric Cancer Registration Trials: A US Food and Drug Administration Perspective
- Journal of the National Cancer Institute (2021) Advancing Assessment, Analysis, and Reporting of Safety and Tolerability in Cancer Trials